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‘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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The fungus among us: use of white rot fungi to biodegrade environmental pollutan...
The fungus among us: use of white rot fungi to biodegrade environmental pollutants.
Environmental Health Perspectives. 1993 Aug; 101(3)232
Confronting Zoonoses, Linking Human and Veterinary Medicine
Confronting Zoonoses, Linking Human and Veterinary Medicine
Emerging Infectious Diseases. 2006 Apr; 12(4)556
Identification of neurotransmitters and co-localization of transmitters in brain...
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 Ã… 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 Ã… 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 Ã…). 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.
Donlan RM, Costerton JW
Clin Microbiol Rev. 2002 Apr; 15(2):167-93.
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Synergistic and Antagonistic Effects of Metal Nanoparticles in Combination with Antibiotics Against Some Reference Strains of Pathogenic Microorganisms.[Infect Drug Resist. 2020]
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One-dimensional colloidal gold and silver nanostructures.[Inorg Chem. 2006]
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Facile Synthesis of Monodisperse Silver Nanospheres in Aqueous Solution via Seed-Mediated Growth Coupled with Oxidative Etching.[Langmuir. 2018]See more ...
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Review Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications.[Chem Rev. 2019]
Comparison of nanosecond and femtosecond pulsed laser deposition of silver nanoparticle films.[Nanotechnology. 2014]
Review A review on biosynthesis of silver nanoparticles and their biocidal properties.[J Nanobiotechnology. 2018]
Review Silver nanoparticles: An integrated view of green synthesis methods, transformation in the environment, and toxicity.[Ecotoxicol Environ Saf. 2019]
Ultrafine Silver Nanoparticles Embedded in Cyclodextrin Metal-Organic Frameworks with GRGDS Functionalization to Promote Antibacterial and Wound Healing Application.[Small. 2019]
Antimicrobial wound dressing nanofiber mats from multicomponent (chitosan/silver-NPs/polyvinyl alcohol) systems.[Carbohydr Polym. 2014]
Fabrication of porous chitosan films impregnated with silver nanoparticles: a facile approach for superior antibacterial application.[Colloids Surf B Biointerfaces. 2010]
Review Klebsiella pneumoniae infection biology: living to counteract host defences.[FEMS Microbiol Rev. 2019]
Synthesis of novel cellulose- based antibacterial composites of Ag nanoparticles@ metal-organic frameworks@ carboxymethylated fibers.[Carbohydr Polym. 2018]
Antibacterial activity and mechanism of silver nanoparticles on Escherichia coli.[Appl Microbiol Biotechnol. 2010]
Negligible particle-specific antibacterial activity of silver nanoparticles.[Nano Lett. 2012]
Review Alternative antimicrobial approach: nano-antimicrobial materials.[Evid Based Complement Alternat Med. 2015]
Review Responsive and Synergistic Antibacterial Coatings: Fighting against Bacteria in a Smart and Effective Way.[Adv Healthc Mater. 2019]
Review Potential antibacterial mechanism of silver nanoparticles and the optimization of orthopedic implants by advanced modification technologies.[Int J Nanomedicine. 2018]
Synergistic antibacterial activity of chitosan-silver nanocomposites on Staphylococcus aureus.[Nanotechnology. 2011]
New insights into the bactericidal activity of chitosan-Ag bionanocomposite: the role of the electrical conductivity.[Colloids Surf B Biointerfaces. 2013]
Antimicrobial Cluster Bombs: Silver Nanoclusters Packed with Daptomycin.[ACS Nano. 2016]
Review Chitosan as antimicrobial agent: applications and mode of action.[Biomacromolecules. 2003]
Review Antimicrobial properties of chitosan and mode of action: a state of the art review.[Int J Food Microbiol. 2010]
Review Chitosan based metallic nanocomposite scaffolds as antimicrobial wound dressings.[Bioact Mater. 2018]
Preparation and characterization of chitosan-based nanocomposite films with antimicrobial activity.[J Agric Food Chem. 2006]
The antibacterial properties of a novel chitosan-Ag-nanoparticle composite.[Int J Food Microbiol. 2008]
The synthesis of chitosan-based silver nanoparticles and their antibacterial activity.[Carbohydr Res. 2009]
Synthesis and anti-fungal effect of silver nanoparticles-chitosan composite particles.[Int J Nanomedicine. 2015]
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Fabrication, characterization of chitosan/nanosilver film and its potential antibacterial application.[J Biomater Sci Polym Ed. 2009]
Fabrication of porous chitosan films impregnated with silver nanoparticles: a facile approach for superior antibacterial application.[Colloids Surf B Biointerfaces. 2010]
Chitosan-hyaluronic acid/nano silver composite sponges for drug resistant bacteria infected diabetic wounds.[Int J Biol Macromol. 2013]
Antiviral activity of silver nanoparticle/chitosan composites against H1N1 influenza A virus.[Nanoscale Res Lett. 2013]
Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease.[Sci Rep. 2016]
Nanoformulations and their mode of action in insects: a review of biological interactions.[Drug Chem Toxicol. 2021]
Review Silver nanoparticles as potential antiviral agents.[Molecules. 2011]
Hydroxyapatite coating of titanium implants using hydroprocessing and evaluation of their osteoconductivity.[Bioinorg Chem Appl. 2012]
Review Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions.[Biomatter. 2012]
Nano-composite scaffolds for bone tissue engineering containing silver nanoparticles: preparation, characterization and biological properties.[J Mater Sci Mater Med. 2013]
Preparation, characterization and antimicrobial activity of a bio-composite scaffold containing chitosan/nano-hydroxyapatite/nano-silver for bone tissue engineering.[Int J Biol Macromol. 2011]
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Review Biomaterials based on chitin and chitosan in wound dressing applications.[Biotechnol Adv. 2011]
Review Chitosan as a Wound Dressing Starting Material: Antimicrobial Properties and Mode of Action.[Int J Mol Sci. 2019]
Development of a chitosan-based wound dressing with improved hemostatic and antimicrobial properties.[Biomaterials. 2008]
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Antimicrobial and antibiofilm activity of curcumin-silver nanoparticles with improved stability and selective toxicity to bacteria over mammalian cells.[Med Microbiol Immunol. 2018]
Synergistic antibacterial effects of curcumin modified silver nanoparticles through ROS-mediated pathways.[Mater Sci Eng C Mater Biol Appl. 2019]
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One step synthesis of antimicrobial peptide protected silver nanoparticles: The core-shell mutual enhancement of antibacterial activity.[Colloids Surf B Biointerfaces. 2020]
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Ultrafine Silver Nanoparticles Embedded in Cyclodextrin Metal-Organic Frameworks with GRGDS Functionalization to Promote Antibacterial and Wound Healing Application.[Small. 2019]
Fabrication of porous chitosan films impregnated with silver nanoparticles: a facile approach for superior antibacterial application.[Colloids Surf B Biointerfaces. 2010]
Synthesis of novel cellulose- based antibacterial composites of Ag nanoparticles@ metal-organic frameworks@ carboxymethylated fibers.[Carbohydr Polym. 2018]
Antimicrobial Cluster Bombs: Silver Nanoclusters Packed with Daptomycin.[ACS Nano. 2016]
The antibacterial properties of a novel chitosan-Ag-nanoparticle composite.[Int J Food Microbiol. 2008]
Review Antiseptics and disinfectants: activity, action, and resistance.[Clin Microbiol Rev. 1999]
Synergistic antibacterial effects of curcumin modified silver nanoparticles through ROS-mediated pathways.[Mater Sci Eng C Mater Biol Appl. 2019]
UV Light Assisted Coating Method of Polyphenol Caffeic Acid and Mediated Immobilization of Metallic Silver Particles for Antibacterial Implant Surface Modification.[Polymers (Basel). 2019]
Biomedical Grade Stainless Steel Coating of Polycaffeic Acid via Combined Oxidative and Ultraviolet Light-Assisted Polymerization Process for Bioactive Implant Application.[Polymers (Basel). 2019]
Antibacterial activity of glutathione-coated silver nanoparticles against Gram positive and Gram negative bacteria.[Langmuir. 2012]
One step synthesis of antimicrobial peptide protected silver nanoparticles: The core-shell mutual enhancement of antibacterial activity.[Colloids Surf B Biointerfaces. 2020]
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.
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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 EmÃlia 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 [7–9].
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
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