Blog Archive

Monday, August 2, 2021

08-02-2021-1350 - pgrhnhetgermneander drafting - fungus, amoebaes/protazoas/amobaezoae/etc. granulomatous encephalitis meningitis meningococcus meningosis cyst or no cyst hydrosomes hydrogen metabolism nmc/aero/anaero/? enterotixins/entertix/enteroticks/lysteriolysin/lysin/inflammation/pyogenes/perfingens/gangars/fuls/faes/legionella/voc/bbb/atrop/microbial loop/chrm1 rec/macrophage/t cell/immune upregulation/autoimmune dis/lesions/cyst/stress resistant cyst/acantha/muscar receptor/ACh NT/volt sensitive 'gated' channels/calciums/calsium/C12+/photoautotroph/asxrepro/budding/fission repro/primary amebic meningoencephalitis/expansion propogation sc/env derived sf prop/trophozoite forms mitotic replication/ invade the central nervous system by hematogenous dissemination causing granulomatous amebic encephalitis (GAE)/phagocyte/sterols/amoebae sterols/opiates/secondary metabolites/antitoxins/H2 and acid from fermentation/(base env)/etc.

Superantigens bridge the MHC class II protein on antigen-presenting cells with the T cell receptor on the surface of T cells with a particular Vβ chain. As a consequence, up to 50% of all T cells are activated, leading to massive secretion of proinflammatory cytokines, which produce the symptoms of toxic shock.

Dimintors: Some strains of E. coli produce heat-stable enterotoxins (ST), which are small peptides that are able to withstand heat treatment at 100 °C. receptors on the cell surface affect intracellular signaling pathways. enterotoxins bind and activate membrane-bound guanylate cyclase, intracellular accumulation of cyclic GMP. nt overload salt dys cell dysf cell det. Prion Disease mimetics/simulants/etc..

Membrane-damaging toxins exhibit hemolysin or cytolysin activity etc.

channel tox, integratory tox (post cell formation), formation modulation tox (cellular), degenerators (metabolite production, component production part, unit production complete whole, etc.)

All CDCs are secreted by the type II secretion system;[4] the exception is pneumolysin, which is released from the cytoplasm of Streptococcus pneumoniae when the bacteria lyse.

The CDCs Streptococcus pneumoniae Pneumolysin, Clostridium perfringens perfringolysin O, and Listeria monocytogenes listeriolysin O cause specific modifications of histones in the host cell nucleus, resulting in down-regulation of several genes that encode proteins involved in the inflammatory response.[5] Histone modification does not involve the pore-forming activity of the CDCs.

Pneumolysins. lysins.

https://en.wikipedia.org/wiki/Exotoxin

Pneumolysin is a putative virulence factor of the Gram-positive bacteria Streptococcus pneumoniae.[1]

It is a pore-forming toxin of 53 kDa composed of 471 amino acids.[2] It has a range of biological activity, including the ability to lyse[3] and interfere with the function of cells and soluble molecules of the immune system.[4]

Released pneumolysin will aid the bacteria during colonization, by facilitating adherence to the host,[5]during invasion by damaging host cells,[6] and during infection by interfering with the host immune response.[7]

The presence of pneumolysin in sputum,[8] urine,[9] CSF[10] and blood[11] can be indicative of an S. pneumoniae infection.

https://en.wikipedia.org/wiki/Pneumolysin

Streptococcus pyogenes is a species of Gram-positive, aerotolerant bacterium in the genus Streptococcus. These bacteria are extracellular, and made up of non-motile and non-sporing cocci. It is clinically important for humans. It is an infrequent, but usually pathogenic, part of the skin microbiota. It is the predominant species harboring the Lancefield group A antigen, and is often called group A Streptococcus (GAS). However, both Streptococcus dysgalactiae and the Streptococcus anginosusgroup can possess group A antigen. Group A streptococci when grown on blood agar typically produces small zones of beta-hemolysis, a complete destruction of red blood cells. (A zone size of 2–3 mm is typical.) It is thus also called group A (beta-hemolytic) Streptococcus (GABHS), and it can make colonies greater than 0.5 mm in size.[1]

https://en.wikipedia.org/wiki/Streptococcus_pyogenes

RTX toxins can be identified by the presence of a specific tandemly repeated nine-amino acid residue sequence in the protein. The prototype member of the RTX toxin family is haemolysin A (HlyA) of E. coli.[citation needed] RTX is also found in Legionella pneumophila.[6]
https://en.wikipedia.org/wiki/Exotoxin

Legionella pneumophila is a thin, aerobic, pleomorphic, flagellated, non-spore-forming, Gram-negative bacterium of the genus Legionella.[1][2] L. pneumophila is the primary human pathogenic bacterium in this group and is the causative agent of Legionnaires' disease, also known as legionellosis.

In nature, L. pneumophila infects freshwater and soil amoebae of the genera Acanthamoeba and Naegleria.[3] The mechanism of infection is similar in amoeba and human cells.


aerobic capable var (metabolic etc. overlap aerobic met resp cap ; no mitochondria or mitochondria - anaerobic or aerobic or both or etc. - hydrosome - hydrogen energy - mitochondria type - mitochondria or not; hydrosome hydrogen metabolism/respiration processes, energy gen by hydrogen (hydrogen decomposer; protein rep for proton; electron current/etc.; energy and processes may use hydrogen only or predom un; etc.) animals pre-mammal mammal type animal type kingdom etc..

https://en.wikipedia.org/wiki/Legionella_pneumophila

Granulomatous Amebic Encephalitis (GAE)[edit]

Granulomatous Amebic Encephalitis (GAE) is caused by amoebic infection of the central nervous system (CNS).

Amaebozoaes

https://en.wikipedia.org/wiki/Acanthamoeba

Acanthamoeba is a genus of amoebae that are commonly recovered from soil, fresh water, and other habitats. Acanthamoeba has two evolutive forms, the metabolically active trophozoite and a dormant, stress-resistant cyst. Trophozoites are small, usually 15 to 25 μm in length and amoeboid in shape. In nature, Acanthamoeba species are free-living bacterivores, but in certain situations, they can cause infections (acanthamebiasis) in humans and other animals.[1]

Infection is generally associated with underlying conditions such as immunodeficiency, diabetes, malignancies, malnutrition, systemic lupus erythematosus, and alcoholism.[1] The parasite enters the body through cuts in the skin or by being inhaled into the upper respiratory tract.[1] The parasite then spreads through the blood into the CNS. Acanthamoeba crosses the blood–brain barrierby means that are not yet understood. Subsequent invasion of the connective tissue and induction of pro-inflammatory responses leads to neuronal damage that can be fatal within days. Pure granulomatous lesions are rare in patients with AIDS and other related immunodeficiency states, as the patients do not have adequate numbers of CD+ve T-cells to mount a granulomatous response to Acanthamoeba infection in CNS and other organs and tissues.[4] A perivascular cuffing with amoebae in necrotic tissue is usual finding in the AIDS and related T-cell immunodeficiency conditions.

Brain biopsy normally reveals severe oedema and hemorrhagic necrosis.[7]

Recent publications show atropine to interfere with the protist's CHRM1 receptor, causing cell death.[9]

Atropine

Infection usually mimics that of bacterial leptomeningitis, tuberculous meningitis, or viral encephalitis. The misdiagnosis often leads to erroneous, ineffective treatment. In the case that the Acanthamoeba is diagnosed correctly, the current treatments, such as amphotericin B, rifampicin, trimethoprim-sulfamethoxazole, ketoconazole, fluconazole, sulfadiazine, or albendazole, are only tentatively successful.

Several species of bacteria that can cause human disease are also able to infect and replicate within Acanthamoeba species.[1] These include Legionella pneumophila, Pseudomonas aeruginosa, and some strains of Escherichia coli and Staphylococcus aureus.[1][15] For some of these bacteria, replication inside Acanthamoeba has been associated with enhanced growth in macrophages, and increased resistance to some antibiotics.[1] Furthermore, due to the high prevalence of Acanthamoeba in the environment, these amoebae have been proposed to serve as an environmental reservoir for some human pathogens.[1]

A. castellanii can be found at high densities in various soil ecosystems. It preys on bacteria, but also fungi and other protozoa.

This species is able to lyse bacteria and produce a wide range of enzymes, such as cellulases or chitinases,[16] and probably contributes to the breakdown of organic matter in soil, contributing to the microbial loop.

Because Acanthamoeba does not differ greatly at the ultrastructural level from a mammalian cell, it is an attractive model for cell-biology studies; it is important in cellular microbiology, environmental biology, physiology, cellular interactions, molecular biology, biochemistry, and evolutionary studies, due to the organisms' versatile roles in the ecosystem and ability to capture prey by phagocytosis, act as vectors and reservoirs for microbial pathogens, and to produce serious human infections. In addition, Acanthamoeba has been used extensively to understand the molecular biology of cell motility[17] and cancer cell dormancy by in-depth exploration of the process of encystation.[18]

Acanthamoeba also has served as a model to study the evolution of certain G-proteins. This unicellular eukaryote expresses few GPCRs over its cell membrane that serve vital role for the microorganism, structural homology bioinformatics tools have been used to show the presence of a homolog of human M1-muscarinic receptor in A. castellanii.[20] Blocking these muscarinic receptors in past studies has proven to be amoebicidal in Acanthamoeba spp.[5] More recently, voltage-gated calcium channels in Acanthamoeba spp. (CavAc) have been reported to have similarities with human voltage-gated calcium channels such as TPC-1 and L-type calcium channels and respond to Ca-channel blockers such as loperamide.[21] This model microbe has been studied to understand complex neurodegenerative states including Alzheimer's disease. Scientists have isolated a neurotransmitter acetylcholine in Acanthamoeba and the enzymatic machinery needed for its synthesis.[22]

The giant viruses Mimivirus, Megavirus, and Pandoravirus infect Acanthamoeba.[25]

Members of the genus Acanthamoeba are unusual in serving as hosts for a variety of giant viruses (that have more than 1000 protein-coding genes; for instance, Pandoravirus, which has about 2500 protein-coding genes in its genome).

https://en.wikipedia.org/wiki/Acanthamoeba
Amoeba

Amoebas (Subphylum Sarcodina) are either naked or shelled, with the encased or testate amoebae largely inhabiting freshwater and moist soils.

From: Encyclopedia of Forest Sciences, 2004



Related terms:
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Enzymes
Fungi
Parasites
Mutation
Proteins
DNA
Protozoa
View all Topics
https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/amoeba

An amoeba (/əˈmiːbə/; less commonly spelt ameba or amœba; plural am(o)ebas or am(o)ebae /əˈmiːbi/),[1] often called an amoeboid, is a type of cell or unicellular organism which has the ability to alter its shape, primarily by extending and retracting pseudopods.[2] Amoebae do not form a single taxonomic group; instead, they are found in every major lineage of eukaryotic organisms. Amoeboid cells occur not only among the protozoa, but also in fungi, algae, and animals.[3][4][5][6][7]

Microbiologists often use the terms "amoeboid" and "amoeba" interchangeably for any organism that exhibits amoeboid movement.[8][9]

In older classification systems, most amoebae were placed in the class or subphylumSarcodina, a grouping of single-celled organisms that possess pseudopods or move by protoplasmic flow. However, molecular phylogenetic studies have shown that Sarcodina is not a monophyletic group whose members share common descent. Consequently, amoeboid organisms are no longer classified together in one group.[10]

The best known amoeboid protists are Chaos carolinense and Amoeba proteus, both of which have been widely cultivated and studied in classrooms and laboratories.[11][12] Other well known species include the so-called "brain-eating amoeba" Naegleria fowleri, the intestinal parasite Entamoeba histolytica, which causes amoebic dysentery, and the multicellular "social amoeba" or slime mouldDictyostelium discoideum.

https://en.wikipedia.org/wiki/Amoeba




Free-living amoebae may be "testate" (enclosed within a hard shell), or "naked" (also known as gymnamoebae, lacking any hard covering). The shells of testate amoebae may be composed of various substances, including calcium, silica, chitin, or agglutinations of found materials like small grains of sand and the frustules of diatoms.[15]

https://en.wikipedia.org/wiki/Amoeba

A frustule is the hard and porous cell wall or external layer of diatoms. The frustule is composed almost purely of silica, made from silicic acid, and is coated with a layer of organic substance, which was referred to in the early literature on diatoms as pectin, a fiber most commonly found in cell walls of plants.[1][2] This layer is actually composed of several types of polysaccharides.[3]

https://en.wikipedia.org/wiki/Frustule

Diatoms (diá-tom-os 'cut in half', from diá, 'through' or 'apart', and the root of tém-n-ō, 'I cut')[6]are a major group of algae,[7] specifically microalgae, found in the oceans, waterways and soils of the world. Living diatoms make up a significant portion of the Earth's biomass: they generate about 20 to 50 percent of the oxygen produced on the planet each year,[8][9] take in over 6.7 billion metric tons of silicon each year from the waters in which they live,[10] and constitute nearly half of the organic material found in the oceans. The shells of dead diatoms can reach as much as a half-mile (800 m) deep on the ocean floor, and the entire Amazon basin is fertilized annually by 27 million tons of diatom shell dust transported by transatlantic winds from the African Sahara, much of it from the Bodélé Depression, which was once made up of a system of fresh-water lakes.[11][12]

https://en.wikipedia.org/wiki/Diatom




The genome sequence of Naegleria gruberi (Fritz-Laylin et al. 2010) and published ESTs from Acanthamoeba castellanii(Hug et al. 2010) each provide a strong prediction of an ability to toggle between aerobic and anaerobic modes of metabolism. The physiological interplay between aerobic and anaerobic modes of ATP production has been studied more extensively in the chlorophyte alga Chlamydomonas reinhardtii. Distributed worldwide, this ubiquitous alga is found in a diversity of aquatic, soil and forest environments (Harris 2009). Known more for growing as a photoautotroph, Chlamydomonas nonetheless responds to dark anaerobic conditions by fermenting the plastidic starch that accumulates in the light (Kreuzberg 1984; Mus et al. 2007; Posewitz et al. 2004). In laboratory-grown algae, the end-products of fermentation are formaldehyde, acetate, ethanol, and H2, plus a little malate (Gfeller and Gibbs 1984; Kreuzberg 1984; Mus et al. 2007).
https://www.sciencedirect.com/topics/immunology-and-microbiology/naegleria-gruberi



Enzymatic chokepoints and synergistic drug targets in the sterol biosynthesis pathway of Naegleria fowleri
Wenxu Zhou ,
Anjan Debnath ,
Gareth Jennings,
Hye Jee Hahn,
Boden H. Vanderloop,
Minu Chaudhuri,
W. David Nes,
Larissa M. Podust

Published: September 13, 2018
https://doi.org/10.1371/journal.ppat.1007245



Naegleria fowleri is a free-living amoeba that can also act as an opportunistic pathogen causing severe brain infection, primary amebic meningoencephalitis (PAM), in humans. The high mortality rate of PAM (exceeding 97%) is attributed to (i) delayed diagnosis, (ii) lack of safe and effective anti-N. fowleri drugs, and (iii) difficulty of delivering drugs to the brain. Our work addresses identification of new molecular targets that may link anti-Naegleria drug discovery to the existing pharmacopeia of brain-penetrant drugs. Using inhibitors with known mechanism of action as molecular probes, we mapped the sterol biosynthesis pathway of N. fowleri by GC-MS analysis of metabolites. Based on this analysis, we chemically validated two enzymes downstream to CYP51, sterol C24-methyltransferase (SMT, ERG6) and sterol Δ8−Δ7 -isomerase (ERG2), as potential therapeutic drug targets in N. fowleri. The sterol biosynthetic cascade in N. fowleri displayed a mixture of canonical features peculiar to different domains of life: lower eukaryotes, plants and vertebrates. In addition to the cycloartenol→ergosterol biosynthetic route, a route leading to de novo cholesterol biosynthesis emerged. Isotopic labeling of the de novo-synthesized sterols by feeding N. gruberi trophozoites on the U13C-glucose-containing growth medium identified an exogenous origin of cholesterol, while 7-dehydrocholesterol (7DHC) had enriched 13C-content, suggesting a dual origin of this metabolite both from de novo biosynthesis and metabolism of scavenged cholesterol. Sterol homeostasis in Naegleria may be orchestrated over the course of its life-cycle by a “switch” between ergosterol and cholesterol biosynthesis. By demonstrating the growth inhibition and synergistic effects of the sterol biosynthesis inhibitors, we validated new, potentially druggable, molecular targets in N. fowleri. The similarity of the Naegleria sterol Δ8−Δ7 -isomerase to the human non-opioid σ1 receptor, implicated in human CNS conditions such as addiction, amnesia, pain and depression, provides an incentive to assess structurally diverse small-molecule brain-penetrant drugs targeting the human receptor for anti-Naegleria activity.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007245



Pathogen & Environment

Causal Agents:

Acanthamoeba spp. , are commonly found in lakes, swimming pools, tap water, and heating and air conditioning units. Several species of Acanthamoeba, including A. culbertsoni, A. polyphaga, A. castellanii, A. astronyxis, A. hatchetti, A. rhysodes, A. divionensis, A. lugdunensis, and A. lenticulata are implicated in human disease.



Acanthamoeba spp. have been found in soil; fresh, brackish, and sea water; sewage; swimming pools; contact lens equipment; medicinal pools; dental treatment units; dialysis machines; heating, ventilating, and air conditioning systems; mammalian cell cultures; vegetables; human nostrils and throats; and human and animal brain, skin, and lung tissues. Unlike N. fowleri, Acanthamoeba has only two stages, cysts (1) and trophozoites (2), in its life cycle. No flagellated stage exists as part of the life cycle. The trophozoites replicate by mitosis (nuclear membrane does not remain intact) (3). The trophozoites are the infective forms, although both cysts and trophozoites gain entry into the body (4) through various means. Entry can occur through the eye (5), the nasal passages to the lower respiratory tract (6), or ulcerated or broken skin (7). When Acanthamoeba spp. enters the eye it can cause severe keratitis in otherwise healthy individuals, particularly contact lens users (8). When it enters the respiratory system or through the skin, it can invade the central nervous system by hematogenous dissemination causing granulomatous amebic encephalitis (GAE) (9) or disseminated disease (10), or skin lesions (11) in individuals with compromised immune systems. Acanthamoeba spp. cysts and trophozoites are found in tissue.

Life cycle image and information courtesy of DPDx.

https://www.cdc.gov/parasites/acanthamoeba/pathogen.html


Vol. 21, No. 1, January - June, 2018 Baqai J. Health Sci.


MINI REVIEW

PRIMARY MENINGOENCEPHALITIS CAUSED BY NAEGLERIA FOWLERI: A MINI REVIEW

Hassan Bin-Asif, Syed Abid Ali*
H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, Pakistan
Received: December 12, 2017 Accepted: February 15, 2018

ABSTRACT

The recent outbreak of primary meningoencephalitis caused by free-living amoebae (FLA), Naegleria fowleri, has gained increasing attention due to their confirmed fatality. It is caused by the entrance of contaminated water into nasal passage mainly by ablution practices. The symptoms include severe headache, nausea, vomiting along with fever finally leading to death. FLA other than N. fowleri such as Acanthamoeba and Balamuthia species are also harmful because they are vectors of many bacterial pathogens including Vibrio, Pseudomonas, Legionella, Enterobacter and Mycobacterium species which help them to feed and colonize in environments, thus contributing to their pathogenesis and transferability to their hosts. Pakistan, being an underdeveloped country, faces long-term shortfalls of electricity resulting in serious water scarcity leading to public dependence on stored water resources, which are breeding hubs for FLA. The rationale of the present review is to highlight the importance of N. fowleri and primary meningoencephalitis and to investigate the recent outbreak in Pakistan.

Keywords: Free-living amoeba, Naegleria fowleri, primary meningoencephalitis.

https://applications.emro.who.int/imemrf/Baqai_J_Health_Sci/Baqai_J_Health_Sci_2018_21_1_42_48.pdf

https://en.wikipedia.org/wiki/Streptococcus_pyogenes
https://en.wikipedia.org/wiki/Exotoxin
https://en.wikipedia.org/wiki/ESKAPE
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305969/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306300/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768623/

08-02-2021-1350 - pgrhnhetgermneander drafting - fungus, amoebaes/protazoas/amobaezoae/etc. granulomatous encephalitis meningitis meningococcus meningosis cyst or no cyst hydrosomes hydrogen metabolism nmc/aero/anaero/? enterotixins/entertix/enteroticks/lysteriolysin/lysin/inflammation/pyogenes/perfingens/gangars/fuls/faes/legionella/voc/bbb/atrop/microbial loop/chrm1 rec/macrophage/t cell/immune upregulation/autoimmune dis/lesions/cyst/stress resistant cyst/acantha/muscar receptor/ACh NT/volt sensitive 'gated' channels/calciums/calsium/C12+/photoautotroph/asxrepro/budding/fission repro/primary amebic meningoencephalitis/expansion propogation sc/env derived sf prop/trophozoite forms mitotic replication/ invade the central nervous system by hematogenous dissemination causing granulomatous amebic encephalitis (GAE)/phagocyte/sterols/amoebae sterols/opiates/secondary metabolites/antitoxins/H2 and acid from fermentation/(base env)/etc.

Hydrozoa (hydrozoans, from ancient Greek ὕδωρ, hydōr, "water" and ζῷον, zōion, "animal") are a taxonomic class of individually very small, predatory animals, some solitary and some colonial, most living in salt water. The colonies of the colonial species can be large, and in some cases the specialized individual animals cannot survive outside the colony. A few genera within this class live in fresh water. Hydrozoans are related to jellyfish and corals and belong to the phylum Cnidaria.

Some examples of hydrozoans are the freshwater jelly (Craspedacusta sowerbyi), freshwater polyps (Hydra), Obelia, Portuguese man o' war (Physalia physalis), chondrophores (Porpitidae), "air fern" (Sertularia argentea), and pink-hearted hydroids (Tubularia).

https://en.wikipedia.org/wiki/Hydrozoa

'amoebaes are carnivorous animals' (dr. bettey dvm, est 2000s)

Myxosporea is a class of microscopic parasites, belonging to the Myxozoa clade within Cnidaria. They have a complex life cycle which comprises vegetative forms in two hosts, an aquatic invertebrate(generally an annelid) and an ectothermic vertebrate, usually a fish. Each host releases a different type of spore. The two forms of spore are so different that until relatively recently they were treated as belonging to different classes within the Myxozoa.

https://en.wikipedia.org/wiki/Myxosporea

iochimie

. 1978;60(3):297-305. doi: 10.1016/s0300-9084(78)80826-8.
Hydrogen metabolism in aerobic hydrogen-oxidizing bacteria
B Schink, H G Schlegel
PMID: 667183
DOI: 10.1016/s0300-9084(78)80826-8

Abstract

A survey on organisms able to use molecular hydrogen as electron donor in the energy-yielding process is presented. In the group of the aerobic hydrogen-oxidizing bacteria so far two types of hydrogenases have been encountered, a NAD-reducing, soluble enzyme (H2 : NAD oxidoreductase) and a membrane-bound enzyme unable to reduce pyridine nucleotides. With respect to the distribution of both types of hydrogenases three groups of hydrogen-oxidizing bacteria can be diffentiated containing (i) both types (Alcaligenes eutrophus), (ii) a soluble enzyme only (Nocardia opaca lb), and (iii) a membrane-bound hydrogenase only (majority of genera and species). The results of studies on the NAD-specific hydrogenase of A. eutrophus are summarized. Results on the solubilization and purification of the membrane-bound hydrogenase of A. eutrophus are presented in detail. The enzyme was solubilized from purified membranes by Triton X-100 and sodium desoxycholate or phospholipase D. The crude membrane extract was fractionated by ammonium sulfate precipitation and chromatography on carboxymethylcellulose at pH 5.5. The enzyme was stable in potassium phosphate buffer; it resembles the soluble enzyme with respect to stability under oxidizing conditions. Further biochemical and immunological data indicate, however, that both enzymes are different with respect to their native structure.

https://pubmed.ncbi.nlm.nih.gov/667183/

EDITORIAL article
Front. Microbiol., 30 January 2020 | https://doi.org/10.3389/fmicb.2020.00056

Editorial: Microbial Hydrogen Metabolism
https://www.frontiersin.org/articles/10.3389/fmicb.2020.00056/full




Journal of Photochemistry and Photobiology B: Biology
Volume 47, Issue 1, November 1998, Pages 1-11

Invited reviewHydrogen metabolism in organisms with oxygenic photosynthesis: hydrogenases as important regulatory devices for a proper redox poising?
Author links open overlay panelJensAppelRüdigerSchulz
https://www.sciencedirect.com/science/article/abs/pii/S1011134498001791



hydrosome

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Definitions

from The Century Dictionary.
noun Same as hydrosoma
from the GNU version of the Collaborative International Dictionary of English.
noun (Zoöl.) All the zooids of a hydroid colony collectively, including the nutritive and reproductive zooids, and often other kinds.
https://www.wordnik.com/words/hydrosome


5 September 2007Hydrosomes: optically trapped water droplets as nano-containers
Kristian Helmerson, Joseph E. Reiner, Alice M. Crawford, Ana M. Jofre, Rani B. Kishore, Lori S. Goldner, Jianyong Tang, Mark E. Greene, Michael Gilson
Author Affiliations +
Proceedings Volume 6644, Optical Trapping and Optical Micromanipulation IV; 66440D (2007) https://doi.org/10.1117/12.735261
Event: NanoScience + Engineering, 2007, San Diego, California, United States

ARTICLE
CITED BY

Abstract
We demonstrate a novel technique for creating, manipulating, and combining femtoliter to attoliter volume chemical containers. Possible uses include creating controlled chemical reactions involving small quantities of reagent, and studying the dynamics of single molecules. The containers, which we call hydrosomes, are surfactant stabilized aqueous droplets in a low index-of-refraction fluorocarbon medium. The index of refraction mismatch between the container and fluorocarbon is such that individual hydrosomes can be optically trapped by single focus laser beams, i.e. optical tweezers. Previous work on single molecules usually involved the tethering of the molecule to a surface, in order to interrogate the molecule for an extended period of time. The use of hydrosomes opens up the possibility for studying free molecules, away from any perturbing surface. We show that this is indeed true in the case of quantitative FRET with RNA. Furthermore, we demonstrate the controlled fusion of two hydrosomes for studying reactions, such as DNA binding kinetics, and single molecule dynamics under non-equilibrium conditions. We also show the applicability of our technique in analytical chemistry, such as for molecule identification and sorting.
© (2007) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
Citation Download Citation

Kristian Helmerson, Joseph E. Reiner, Alice M. Crawford, Ana M. Jofre, Rani B. Kishore, Lori S. Goldner,Jianyong Tang, Mark E. Greene, and Michael Gilson "Hydrosomes: optically trapped water droplets as nano-containers", Proc. SPIE 6644, Optical Trapping and Optical Micromanipulation IV, 66440D (5 September 2007); https://doi.org/10.1117/12.735261
ACCESS THE FULL ARTICLE
https://www.spiedigitallibrary.org/conference-proceedings-of-spie/6644/66440D/Hydrosomes-optically-trapped-water-droplets-as-nano-containers/10.1117/12.735261.short?SSO=1

Cases
199,000,000
Recovered
-
Deaths
4,240,000
LocationCasesRecoveredDeaths
United States
35,200,000
+136,000
-
613,000
+454
India
31,700,000
+30,549
30,900,000
+38,887
425,000
+422
Brazil
20,000,000
+15,143
17,800,000
557,000
+389
Russia
6,230,000
+22,969
5,570,000
+14,701
https://en.wikipedia.org/wiki/Template:COVID-19_pandemic_data



08-02-2021-1219 - Fun With Guys Funguys Fungies - Fungus and Decaying Matter and Decay Facilitation (Decomposition of Biological Materials and Semi-Biological Materials - e.g. wood, leaves, insect carcas, paint, drugs, tissue, etc.) - the intelligent decomposer - hydrogen antibiotics - nuclear particle gas anti-organismals - hydrogen gas antiorganismals-ion antiorganismals etc. - mechanical inducer antiorganismals - nuclear antiorganismals - geoantiorganismals 831

Dr. Beatteys, Bob:

Fun With Guys

Funguys

Fungies

‘Black Fungus’ Is Appearing in People with COVID-19: What to Know
Rondello pointed out that there is “mounting recognition” of a condition called coronavirus disease–associated pulmonary aspergillosis (CAPA).
https://www.healthline.com/health-news/black-fungus-is-appearing-in-people-with-covid-19-what-to-know

Environ Health Perspect. 1993 Aug; 101(3): 232–233.
doi: 10.1289/ehp.93101232

The fungus among us: use of white rot fungi to biodegrade environmental pollutants.
S D Aust and J T Benson

PMCID: PMC1519769
PMID: 8404759

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1519769/



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Identification of neurotransmitters and co-localization of transmitters in brainstem respiratory neurons
NIHPA Author Manuscripts. 2008 Dec 10; 164(1-2)18

Bone composition: relationship to bone fragility and antiosteoporotic drug effec...
Bone composition: relationship to bone fragility and antiosteoporotic drug effects
BoneKEy Reports. 2013; 2()

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and application...

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Feb 1; 61(Pt 2): 205–207.
Published online 2005 Jan 20. doi: 10.1107/S1744309104034463

Crystallization and preliminary structure analysis of the blue laccase from the ligninolytic fungus Panus tigrinus
Marta Ferraroni,a Ilaria Duchi,a Nina M. Myasoedova,b Alexey A. Leontievsky,b Ludmila A. Golovleva,bAndrea Scozzafava,a and Fabrizio Brigantia,*
Author information Article notes Copyright and License information Disclaimer
This article has been cited by other articles in PMC.
PMCID: PMC1952268
PMID: 16510995
The blue laccase from the white-rot basidiomycete fungus Panus tigrinus, an enzyme involved in lignin biodegradation, has been crystallized.
The blue laccase from the white-rot basidiomycete fungus Panus tigrinus, an enzyme involved in lignin biodegradation, has been crystallized. P. tigrinus laccase crystals grew within one week at 296 K using the sitting-drop vapour-diffusion method in 22%(w/v) PEG 4000, 0.2 M CaCl2, 100 mM Tris–HCl pH 7.5. The crystals belong to the monoclinic space group P21, with unit-cell parameters a = 54.2, b = 111.6, c = 97.1, β = 97.7°, and contain 46% solvent. A complete native data set was collected to 1.4 Å resolution at the copper edge. Molecular replacement using the Coprinus cinereus laccase structure (PDB code http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1hfu) as a starting model was performed and initial electron-density maps revealed the presence of a full complement of copper ions. Model refinement is in progress. The P. tigrinuslaccase structural model exhibits the highest resolution available to date and will assist in further elucidation of the catalytic mechanism and electron-transfer processes for this class of enzymes.

White-rot fungi degrade wood lignin using a combination of special­ized intracellular and extracellular enzymes (Leonowicz et al., 1999). Lignin, the most common polymer on earth, which provides the structural component of the plant cell wall, is a heterogeneous biopolymer composed of phenyl propanoid units linked by various non-hydrolyzable C—C and C—O bonds (Lewis et al., 1998).


The most prominent representatives of this family include ascorbate oxidase and mammalian plasma ceruloplasmin (Messerschmidt, 1997; Messerschmidt & Huber, 1990; Solomon et al., 1996). These multi-copper enzymes contain four Cu atoms per molecule, which are organized into three different copper sites that catalyze the one-electron oxidation of four reducing-substrate molecules concomitant with the four-electron reduction of molecular oxygen to water molecules. Blue copper oxidases contain at least one type-1 copper, which is presumably the primary oxidation site, whereas blue multi-copper oxidases typically employ at least three additional coppers: one type-2 and two type-3 copper ions arranged in a trinuclear cluster, the latter being the site where the reduction of molecular oxygen occurs.

A broad range of substrates such as polyphenols, methoxy-substituted phenols, diamines and particular inorganic compounds are generally oxidized through the catalytic action of laccases and, as reported above, synthetic or natural mediator molecules can further enlarge their range of action (Xu, 1996).

Biotechnological research on laccases, aiming towards the development of industrial processes such as pulp delignification and removal of environmental pollutants, for example pesticides and textile dyes, from contaminated soil and water, is currently being performed (Aust & Benson, 1993; Murugesan & Kalaichelvan, 2003). In order to optimize these promising processes, complete understanding of the catalytic mechanism of laccases and in particular of their redox potential and substrate-selectivity control are needed; detailed characterization of the high-resolution molecular structure of such enzymes will surely help in achieving these aims.

Several crystal structures of laccases have been solved recently. At first, extensive microheterogeneity, which is presumably caused by the variable glycosylation of these enzymes, hindered successful crystallization, but performing deglycosylation in order to enable the production of high-quality diffracting crystals resulted in loss of copper, as in the case of Ducros et al. (1998), who reported the crystal structure of a laccase from the fungus Coprinus cinereus at 1.68 Å resolution in a form devoid of the type-2 copper and therefore in a catalytically incompetent state.

The preliminary density maps revealed the presence of a full complement of copper ions and several complex carbohydrate moieties.

The blue laccase was purified to apparent electrophoretic homogeneity as reported and was used for subsequent crystallization experiments. Laccase activity was determined quantitatively by monitoring the oxidation of 0.2 mMABTS [2,2′-azinobis(3-ethylbenzthiazolinesulfonic acid)] at 420 nm (extinction coefficient 36 000 mM −1 cm−1) in the presence of 20 mM sodium acetate pH 5.0 at 293 K.

P. tigrinus blue laccase crystals were harvested from mother liquor utilizing cryoloops and soaked for 1–2 min in a solution consisting of the same mother-liquor solution with the addition of 10%(v/v) glycerol. The crystal mounted in a suitable cryoloop was flash-cooled in a nitrogen-gas stream at 100 K.

Diffraction data were collected at the European Molecular Biology Laboratory (EMBL) beamline BW7A at the DORIS storage ring of the Deutsches Elektronen Synchrotron (DESY), Hamburg using a MAR CCD system at the copper edge (1.377 Å). A total of 340 diffraction images were recorded at a crystal-to-detector distance of 50 mm.

After collecting the diffraction data, some of the crystals were dissolved in 20 mM sodium acetate buffer pH 5.0 and tested for activity as described above. They showed complete retention of the initial activity.

Under the optimal conditions (see §2), crystals of laccase from P. tigrinus grew within one week at 296 K using the sitting-drop vapour-diffusion method to approximate dimensions of 0.2 × 0.2 × 0.8 mm (see Fig. 1). Table 1 gives a summary of data collection and processing.

The P. tigrinus blue laccase structural model will assist in the further elucidation of the catalytic mechanism and electron-transfer processes for this class of enzymes.


Keywords: laccases, phenol oxidases, multicopper oxidases, lignin

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1952268/

BlueGus
VBT


Pathog Glob Health. October, 2015; 109(7): 309–318.
doi: 10.1179/2047773215Y.0000000030

Antimicrobial resistance: a global multifaceted phenomenon
Francesca Prestinaci,* Patrizio Pezzotti, and Annalisa Pantosti
Author information Article notes Copyright and License information Disclaimer
This article has been cited by other articles in PMC.


Antimicrobial resistance (AMR) is one of the most serious global public health threats in this century. The first World Health Organization (WHO) Global report on surveillance of AMR, published in April 2014, collected for the first time data from national and international surveillance networks, showing the extent of this phenomenon in many parts of the world and also the presence of large gaps in the existing surveillance. In this review, we focus on antibacterial resistance (ABR), which represents at the moment the major problem, both for the high rates of resistance observed in bacteria that cause common infections and for the complexity of the consequences of ABR. We describe the health and economic impact of ABR, the principal risk factors for its emergence and, in particular, we illustrate the highlights of four antibiotic-resistant pathogens of global concern – Staphylococcus aureus, Klebsiella pneumoniae, non-typhoidal Salmonella and Mycobacterium tuberculosis – for whom we report resistance data worldwide. Measures to control the emergence and the spread of ABR are presented.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768623/

From Supramolecular Hydrogels to Multifunctional Carriers for Biologically Active Substances
Joanna Skopinska-Wisniewska,1 Silvia De la Flor,2 and Justyna Kozlowska1,*
M. Sheikh Mohamed, Academic Editor and Toru Maekawa, Academic Editor
Author information Article notes Copyright and License information Disclaimer
Int J Mol Sci. 2021 Jul; 22(14): 7402.
Published online 2021 Jul 9. doi: 10.3390/ijms22147402

Supramolecular hydrogels are 3D, elastic, water-swelled materials that are held together by reversible, non-covalent interactions, such as hydrogen bonds, hydrophobic, ionic, host–guest interactions, and metal–ligand coordination. These interactions determine the hydrogels’ unique properties: mechanical strength; stretchability; injectability; ability to self-heal; shear-thinning; and sensitivity to stimuli, e.g., pH, temperature, the presence of ions, and other chemical substances. For this reason, supramolecular hydrogels have attracted considerable attention as carriers for active substance delivery systems. In this paper, we focused on the various types of non-covalent interactions. The hydrogen bonds, hydrophobic, ionic, coordination, and host–guest interactions between hydrogel components have been described. We also provided an overview of the recent studies on supramolecular hydrogel applications, such as cancer therapy, anti-inflammatory gels, antimicrobial activity, controlled gene drug delivery, and tissue engineering.
Keywords: supramolecular hydrogels, non-covalent interactions, drug delivery, controlled release
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307912/

Nanomaterials (Basel). 2021 Jul; 11(7): 1687.
Published online 2021 Jun 27. doi: 10.3390/nano11071687
PMCID: PMC8306300
PMID: 34199123

Ag-Based Synergistic Antimicrobial Composites. A Critical Review
Ekaterina A. Kukushkina,1,2 Syed Imdadul Hossain,1,2 Maria Chiara Sportelli,1,2 Nicoletta Ditaranto,1,2Rosaria Anna Picca,1,2 and Nicola Cioffi1,2,*
Angela Ivask, Academic Editor
Author information Article notes Copyright and License information Disclaimer

Abstract

The emerging problem of the antibiotic resistance development and the consequences that the health, food and other sectors face stimulate researchers to find safe and effective alternative methods to fight antimicrobial resistance (AMR) and biofilm formation. One of the most promising and efficient groups of materials known for robust antimicrobial performance is noble metal nanoparticles. Notably, silver nanoparticles (AgNPs) have been already widely investigated and applied as antimicrobial agents. However, it has been proposed to create synergistic composites, because pathogens can find their way to develop resistance against metal nanophases; therefore, it could be important to strengthen and secure their antipathogen potency. These complex materials are comprised of individual components with intrinsic antimicrobial action against a wide range of pathogens. One part consists of inorganic AgNPs, and the other, of active organic molecules with pronounced germicidal effects: both phases complement each other, and the effect might just be the sum of the individual effects, or it can be reinforced by the simultaneous application. Many organic molecules have been proposed as potential candidates and successfully united with inorganic counterparts: polysaccharides, with chitosan being the most used component; phenols and organic acids; and peptides and other agents of animal and synthetic origin. In this review, we overview the available literature and critically discuss the findings, including the mechanisms of action, efficacy and application of the silver-based synergistic antimicrobial composites. Hence, we provide a structured summary of the current state of the research direction and give an opinion on perspectives on the development of hybrid Ag-based nanoantimicrobials (NAMs).
Keywords: silver nanoparticles, hybrid materials, nanocomposites, antimicrobials, synergistic, silver conjugates, chitosan


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306300/



w Biofilms: survival mechanisms of clinically relevant microorganisms.
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Biomedical Grade Stainless Steel Coating of Polycaffeic Acid via Combined Oxidative and Ultraviolet Light-Assisted Polymerization Process for Bioactive Implant Application.[Polymers (Basel). 2019]


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The internal environment is rich with proteins, sugars and nucleic acids and is able to keep bacteria in close vicinity, providing safe and advantageous, tight, cell-to-cell interaction and DNA exchange [9,10]. Recently, it has been found that it is possible to encode light-induced, membrane-potential-based memory-patterns within bacteria in intimate contact as a biofilm [11]. Besides the noxious impact on food, water quality and health care industry, biofilms can serve as a useful and sustainable alternative to provide a low-cost source of power and clean sustainable energy or even act beneficially during cost-effective and sustainable water treatment procedures for some types of filters [12].

'biofilms can serve as a useful and sustainable alternative to provide a low-cost source of power and clean sustainable energy or even act beneficially during cost-effective and sustainable water treatment procedures for some types of filters [12]'
'Notably, silver nanoparticles (AgNPs) have been already widely investigated and applied as antimicrobial agents. However, it has been proposed to create synergistic composites, because pathogens can find their way to develop resistance against metal nanophases;'

Nanomaterials (Basel). 2021 Jul; 11(7): 1687.
Published online 2021 Jun 27. doi: 10.3390/nano11071687
PMCID: PMC8306300
PMID: 34199123
Ag-Based Synergistic Antimicrobial Composites. A Critical Review
Ekaterina A. Kukushkina,1,2 Syed Imdadul Hossain,1,2 Maria Chiara Sportelli,1,2 Nicoletta Ditaranto,1,2Rosaria Anna Picca,1,2 and Nicola Cioffi1,2,*


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306300/


hydrogen antibio gas


08-02-2021-1219 - Fun With Guys Funguys Fungies - Fungus and Decaying Matter and Decay Facilitation (Decomposition of Biological Materials and Semi-Biological Materials - e.g. wood, leaves, insect carcas, paint, drugs, tissue, etc.) - the intelligent decomposer - hydrogen antibiotics - nuclear particle gas anti-organismals - hydrogen gas antiorganismals-ion antiorganismals etc. mechanical inducer anti-organismals - etc.

bromine iodine lead phosphorous arsenic silver negative ions anions particule-atom nuclear particle energy field electro-proto light particle gas (phonon cult photon cult processed molecules released conditioned eye/system large scale)


hydrogen-deuterium-hydrogen cats-oxygen dimers-ozone-ozole-potas-tar-marble-slate-salt-sulphene-nitrane-trihydrocat-hygroscopantsfieldaberrs-voc-voc chain cascade dominos tunnel channel chaining chunking etc. (e.g. steam engine train ops) -


Sublimination-Spont Combustion-Disintegration-Hygroscopants-Dessicants(MM)[vbt]-Reactive to water- Air Unstable-Floor Heaters-Mirrors-Light Imaging-Particle Imaging-Particle signal transmission/transformation/transferrence/etc.-contact explosives-hydrophobicity-anti hydrophiles-steam-pressure-energy-transform-state change-mechanical-space or time corruptions etc.-cause=effect-etc.;
https://en.wikipedia.org/wiki/Desiccant

Space-Time corruptions result in surprising outcome (steam engine train moves).


Space or time corruption explosive surprise outerspace; matrice build quickly and shift in larger space unrelated may facilitate collapse of matric; energy exceeded for construction or stunt point and implosion or explosion


Plane deformation enabled new molecule design

Molecules. 2021 Jul; 26(14): 4253.
Published online 2021 Jul 13. doi: 10.3390/molecules26144253
PMCID: PMC8305969
PMID: 34299528
Synthesis, Antibacterial and Antifungal Activity of New 3-Aryl-5H-pyrrolo[1,2-a]imidazole and 5H-Imidazo[1,2-a]azepine Quaternary Salts
Sergii Demchenko,1 Roman Lesyk,2,* Oleh Yadlovskyi,1 Johannes Zuegg,3 Alysha G. Elliott,3 Iryna Drapak,4Yuliia Fedchenkova,5 Zinaida Suvorova,1 and Anatolii Demchenko1,5
Athina Geronikaki, Academic Editor and Maria Emília de Sousa, Academic Editor
Author information Article notes Copyright and License information Disclaimer


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305969/

ESKAPE group pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306300/


Biomed Res Int. 2016; 2016: 2475067.
Published online 2016 May 5. doi: 10.1155/2016/2475067
PMCID: PMC4871955
PMID: 27274985
Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens
Sirijan Santajit and Nitaya Indrawattana *
Author information Article notes Copyright and License information Disclaimer


2. Antimicrobial Resistance Mechanisms of ESKAPE Pathogens

Antimicrobial resistance genes may be carried on the bacterial chromosome, plasmid, or transposons [6]. Mechanisms of drug resistance fall into several broad categories, including drug inactivation/alteration, modification of drug binding sites/targets, changes in cell permeability resulting in reduced intracellular drug accumulation, and biofilm formation [79].


Nosocomial infections are caused by a variety of organisms, including bacteria, fungi, viruses, parasites, and other agents.
the Ambler scheme (molecular classification) and the Bush-Jacoby-Medeiros system, which classifies the most clinically important β-lactamases as those produced by Gram-negative bacteria [4]. Ambler class A enzymes consist of penicillinase, cephalosporinase, broad-spectrum β-lactamases, extended-spectrum β-lactamases (ESBLs), and carbapenemases. They can inactivate penicillins (except temocillin), third-generation oxyimino-cephalosporins (e.g., ceftazidime, cefotaxime, and ceftriaxone), aztreonam, cefamandole, cefoperazone, and methoxy-cephalosporins (e.g., cephamycins and carbapenems). Class A enzymes can also be inhibited by β-lactamase inhibitors, such as clavulanic acid, sulbactam, or tazobactam [5, 6].

Carbapenemases are also prevalent in clinical bacterial isolates such as K. pneumonia such as KPC-1 that results in resistance to imipenem, meropenem, amoxicillin/clavulanate, piperacillin/tazobactam, ceftazidime, aztreonam, and ceftriaxone [14].
Amongst sulfhydryl variable (SHV) enzymes, SHV-1 is the most clinically relevant and represents the most common K. pneumoniae [11]. The genes coding for TEM and SHV enzymes have quite high mutation rates, resulting in a high level of diversity in enzyme types and thus increasing the scope of antibiotic resistance.
Class A enzymes can also be inhibited by β-lactamase inhibitors, such as clavulanic acid, sulbactam, or tazobactam [5, 6].
They can inactivate penicillins (except temocillin), third-generation oxyimino-cephalosporins (e.g., ceftazidime, cefotaxime, and ceftriaxone), aztreonam, cefamandole, cefoperazone, and methoxy-cephalosporins (e.g., cephamycins and carbapenems).
However, by changing the peptidoglycan cross-link target (D-Ala-D-Ala to D-Ala-D-Lac or D-Ala-D-Ser), encoded by a complex gene cluster (Van-A, Van-B, Van-D, Van-C, Van-E, and Van-G), E. faecium and E. faecalis can increase their resistance to glycopeptides in current clinical use (vancomycin and teicoplanin) [6].
The balance of antibiotic uptake and elimination determines the susceptibility of bacteria to a particular drug. Thus, reducing the amount of antibiotic able to pass through the bacterial cell membrane is one strategy used by bacteria to develop antibiotic resistance. Mechanisms by which bacteria achieve this include the occurrence of diminished protein channels on the bacterial outer membrane to decrease drug entry and/or the presence of efflux pumps to decrease the amount of drug accumulated within the cells.
It could be argued that the main causes of antimicrobial resistance are not classical drug resistance mechanisms, that is, efflux pumps, target site modification, or enzymatic degradation. It is likely that the matrix of biofilms provides a mechanical and biochemical shield that provides the conditions needed to attenuate the activity of the drugs (e.g., low O2, low pH, high CO2, and low water availability).
Enterococcus species were formerly classified as part of the genus Streptococcus. They are Gram-positive facultative anaerobes, which are often found in pairs or chains. Their normal habitat is the gut of humans and animals. There are more than 20 Enterococcus species, but Enterococcus faecium and Enterococcus faecalis are the most clinically relevant. Most Enterococcus infections are endogenously acquired, but cross-infection may occur in hospitalized patients [33].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871955/

Curr Opin Microbiol

. 2005 Oct;8(5):518-24. doi: 10.1016/j.mib.2005.08.014.
The threat of antibiotic resistance in Gram-negative pathogenic bacteria: beta-lactams in peril
Jodi M Thomson 1, Robert A Bonomo
Affiliations expand
PMID: 16126451
DOI: 10.1016/j.mib.2005.08.014

Abstract

Beta-lactam antibiotics are the cornerstone of our antibiotic armamentarium. By inhibiting bacterial cell wall synthesis, they are highly effective against Gram-positive and Gram-negative bacteria. Unfortunately, bacteria have evolved sophisticated resistance mechanisms to combat the lethal effects of beta-lactam antibiotics. Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae are all able to evade killing by penicillins, cephalosporins and carbapenems. This multi-drug resistant phenotype that challenges health care workers worldwide is caused by an array of resistance determinants. These include altered expression of outer membrane proteins and efflux pumps, along with an increasing arsenal of beta-lactamases. Future strategies in beta-lactam design must take into account the complex nature of resistance in Gram-negative pathogens.
https://pubmed.ncbi.nlm.nih.gov/16126451/

Eur J Clin Microbiol Infect Dis

. 2000 Jan;19(1):39-42. doi: 10.1007/s100960050007.
Virulence factors of Enterococcus faecalis and Enterococcus faecium blood culture isolates
H A Elsner 1, I Sobottka, D Mack, M Claussen, R Laufs, R Wirth
Affiliations expand
PMID: 10706178
DOI: 10.1007/s100960050007

Abstract

Known and potential virulence factors of enterococcal blood culture isolates were studied using 89 Enterococcus faecalis and 24 Enterococcus faecium isolates. The prevalence of the respective factors was (Enterococcus faecalis vs. Enterococcus faecium): hemolysin 16% vs. 0%, gelatinase 55% vs. 0%, aggregation substance 63% vs. 13%, lipase 35% vs. 4%, hemagglutinin 97% vs. 0%. Deoxyribonuclease was not detected in any isolate. The study showed that hemagglutinin and lipase may represent additional virulence factors of Enterococcus faecalis but not Enterococcus faecium. The significance of these factors in the pathogenesis of enterococcal infection needs to be elucidated in further studies.

https://pubmed.ncbi.nlm.nih.gov/10706178/
Because of natural and unnatural selective pressures and factors, antibiotic resistance in bacteria usually emerges through genetic mutation or acquires antibiotic-resistant genes (ARGs) through horizontal gene transfer - a genetic exchange process by which antibiotic resistance can spread.[7]
https://en.wikipedia.org/wiki/ESKAPE


Diagonal and scale switching gene transfer; geneti trans in time warp; genetic trans in particle; genetic trans in field; genetic trans flash imaging light gas particle or light; genetic trans in alt; genetic trans in anti; genetic trans in diagonal; genetic trans in diamond; genetic trans in seq unlocking w ver; genetic trans in code; gene trans in zig; gene trans in grid; gene trans in spec form; gene trans in fitting; gene trans in spiral; gene trans in globule; gene trans in circ; gene trans in tri or squ; gene trans internal chat; gene trans in nested; gene trans alt state; gene substitute; gene analog; man mad gene; etc.


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Antimicrobial Resistance in ESKAPE Pathogens
Authors: David M. P. De Oliveira, Brian M. Forde https://orcid.org/0000-0002-2264-4785, Timothy J. Kidd, Patrick N. A. Harris, Mark A. Schembri https://orcid.org/0000-0003-4863-9260, Scott A. Beatson https://orcid.org/0000-0002-1806-3283, David L.Paterson, and Mark J. WalkerAUTHORS INFO & AFFILIATIONS
DOI: https://doi.org/10.1128/CMR.00181-19



SUMMARY
Antimicrobial-resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens represent a global threat to human health. The acquisition of antimicrobial resistance genes by ESKAPE pathogens has reduced the treatment options for serious infections, increased the burden of disease, and increased death rates due to treatment failure and requires a coordinated global response for antimicrobial resistance surveillance. This looming health threat has restimulated interest in the development of new antimicrobial therapies, has demanded the need for better patient care, and has facilitated heightened governance over stewardship practices.
https://journals.asm.org/doi/10.1128/CMR.00181-19


Biofilms are a mixture of diverse microbial communities and polymers that protect the bacteria from antibiotic treatment by acting as a physical barrier.[4]
https://en.wikipedia.org/wiki/ESKAPE



An exotoxin is a toxin secreted by bacteria.[1] An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host-pathogen interface.
They may exert their effect locally or produce systemic effects. Well-known exotoxins include: botulinum toxin produced by Clostridium botulinum; Corynebacterium diphtheriae toxin, produced during life-threatening symptoms of diphtheria; tetanospasmin produced by Clostridium tetani. The toxic properties of most exotoxins can be inactivated by heat or chemical treatment to produce a toxoid. These retain their antigenic specificity and can be used to produce antitoxins and, in the case of diphtheria and tetanus toxoids, are used as vaccines.

Type I: cell surface-active[edit]

Type I toxins bind to a receptor on the cell surface and stimulate intracellular signaling pathways. Two examples are described below.
Superantigens[edit]

Superantigens are produced by several bacteria. The best-characterized superantigens are those produced by the strains of Staphylococcus aureus and Streptococcus pyogenes that cause toxic shock syndrome. Superantigens bridge the MHC class II protein on antigen-presenting cells with the T cell receptor on the surface of T cells with a particular Vβ chain. As a consequence, up to 50% of all T cells are activated, leading to massive secretion of proinflammatory cytokines, which produce the symptoms of toxic shock.
Heat-stable enterotoxins[edit]

Some strains of E. coli produce heat-stable enterotoxins (ST), which are small peptides that are able to withstand heat treatment at 100 °C. Different STs recognize distinct receptors on the cell surface and thereby affect different intracellular signaling pathways. For example, STa enterotoxins bind and activate membrane-bound guanylate cyclase, which leads to the intracellular accumulation of cyclic GMP and downstream effects on several signaling pathways. These events lead to the loss of electrolytes and water from intestinal cells.
Type II: membrane damaging[edit]

Membrane-damaging toxins exhibit hemolysin or cytolysin activity in vitro. However, induction of cell lysis may not be the primary function of the toxins during infection. At low concentrations of toxin, more subtle effects such as modulation of host cell signal transduction may be observed in the absence of cell lysis. Membrane-damaging toxins can be divided into two categories, the channel-forming toxins and toxins that function as enzymes that act on the membrane.
Channel-forming toxins[edit]

Most channel-forming toxins, which form pores in the target cell membrane, can be classified into two families: the cholesterol-dependent toxins and the RTX toxins.
Cholesterol-dependent cytolysins

Formation of pores by cholesterol-dependent cytolysins (CDC) requires the presence of cholesterol in the target cell. The size of the pores formed by members of this family is extremely large: 25-30 nm in diameter. All CDCs are secreted by the type II secretion system;[4] the exception is pneumolysin, which is released from the cytoplasm of Streptococcus pneumoniae when the bacteria lyse.

The CDCs Streptococcus pneumoniae Pneumolysin, Clostridium perfringens perfringolysin O, and Listeria monocytogenes listeriolysin O cause specific modifications of histones in the host cell nucleus, resulting in down-regulation of several genes that encode proteins involved in the inflammatory response.[5] Histone modification does not involve the pore-forming activity of the CDCs.
RTX toxins

RTX toxins can be identified by the presence of a specific tandemly repeated nine-amino acid residue sequence in the protein. The prototype member of the RTX toxin family is haemolysin A (HlyA) of E. coli.[citation needed] RTX is also found in Legionella pneumophila.[6]
Enzymatically active toxins[edit]

One example is the α toxin of C. perfringens, which causes gas gangrene; α toxin has phospholipase activity.
Type III: intracellular[edit]

Type III exotoxins can be classified by their mode of entry into the cell, or by their mechanism once inside.
By mode of entry[edit]

Intracellular toxins must be able to gain access to the cytoplasm of the target cell to exert their effects.
Some bacteria deliver toxins directly from their cytoplasm to the cytoplasm of the target cell through a needle-like structure. The effector proteins injected by the type III secretion apparatus of Yersinia into target cells are one example.
Another group of intracellular toxins is the AB toxins. The 'B'-subunit (binding) attaches to target regions on cell membranes, the 'A'-subunit (active) enters through the membrane and possesses enzymatic function that affects internal cellular bio-mechanisms. A common example of this A-subunit activity is called ADP-ribosylation in which the A-subunit catalyzes the addition of an ADP-ribose group onto specific residues on a protein. The structure of these toxins allows for the development of specific vaccines and treatments. Certain compounds can be attached to the B unit, which is not, in general, harmful, which the body learns to recognize, and which elicits an immune response. This allows the body to detect the harmful toxin if it is encountered later, and to eliminate it before it can cause harm to the host. Toxins of this type include cholera toxin, pertussis toxin, Shiga toxin and heat-labile enterotoxin from E. coli.
By mechanism[edit]

Once in the cell, many of the exotoxins act at the eukaryotic ribosomes (especially 60S), as protein synthesis inhibitors. (Ribosome structure is one of the most important differences between eukaryotes and prokaryotes, and, in a sense, these exotoxins are the bacterial equivalent of antibiotics such as clindamycin.)
Some exotoxins act directly at the ribosome to inhibit protein synthesis. An example is Shiga toxin.
Other toxins act at elongation factor-2. In the case of the diphtheria toxin, EF2 is ADP-ribosylated and becomes unable to participate in protein elongation, and, so, the cell dies. Pseudomonas exotoxin has a similar action.

Other intracellular toxins do not directly inhibit protein synthesis.
For example, Cholera toxin ADP-ribosylates, thereby activating tissue adenylate cyclase to increase the concentration of cAMP, which causes the movement of massive amounts of fluid and electrolytes from the lining of the small intestine and results in life-threatening diarrhea.
Another example is Pertussis toxin.
Extracellular matrix damage[edit]

These "toxins" allow the further spread of bacteria and, as a consequence, deeper tissue infections. Examples are hyaluronidase and collagenase. These molecules, however, are enzymes that are secreted by a variety of organisms and are not usually considered toxins. They are often referred to as virulence factors, since they allow the organisms to move deeper into the hosts tissues.[7]
https://en.wikipedia.org/wiki/Exotoxin