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Growing Resistance with Antibiotics (FT Press Delivers Elements)

As a global community, we have not considered antibiotics as a resource to be actively protected. Consequently, we use antibiotics in ways that directly lead to resistance.


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Changing those ways requires an understanding of antibiotic principles. We begin with a brief description of MRSA to illustrate a bacterial-based health problem…. Advanced Buteyko Breathing Exercises.

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A comprehensive assessment of the impact of all known HSI-I T6SS effectors on biofilm-specific antibiotic resistance could help to further elucidate the role of this secretion system in antibiotic resistance. Biofilm-based infections are difficult to eradicate due to their ability to withstand antibiotic concentrations that would normally kill free-swimming planktonic cells.

As a consequence, bacterial biofilms significantly contribute to morbidity and mortality in patients. As discussed in this review, there are many mechanisms, such as persister cells, stress responses and biofilm heterogeneity, that have been found to contribute to biofilm antibiotic resistance and tolerance. It has also become clear that the underlying mechanisms of antibiotic tolerance and resistance in biofilms have, in many cases, a genetic basis. Additional thoughts for future directions are provided below. As was probably apparent while reading this review, Pseudomonas aeruginosa has been the most extensively studied pathogen when it comes to mechanisms of biofilm tolerance and resistance.

While this review should not be considered to be comprehensive, there is an obvious paucity of papers that specifically describe discrete mechanisms of antibiotic resistance and tolerance in biofilm-forming bacterial pathogens other than P.

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It would be ill advised to assume that other bacteria share the same mechanisms as P. Ideally, biofilm-specific antibiotic resistance and tolerance mechanisms that are unique to specific pathogens will be identified, allowing for the development of therapeutics that selectively target and impair these pathogen-specific mechanisms. Moving forward, it is important that we continue to identify and characterise the mechanisms in bacterial biofilms that promote antibiotic recalcitrance. Modern technology and innovative experimental setups and approaches, such as investigation of the metabolomes of pathogenic bacterial biofilms Zhang and Powers ; Stipetic et al.

The study by Amini et al. Additionally, Amini et al. Most importantly, it is imperative that the determinants of biofilm recalcitrance continue to guide therapeutic strategies that would impair these defences Taylor, Yeung and Hancock By preventing biofilms from surviving high doses of antibiotics, the treatment success rate of biofilm-based infections will be improved and patients will benefit tremendously. The impact of commonly prescribed, non-antimicrobial medications on the modulation of antimicrobial resistance in biofilms is another question that has been minimally explored, although research on this topic could have far-reaching consequences on patient care considering that polypharmacy is quite prevalent in the elderly and in other patient populations who are prone to biofilm-based infections.

Intriguingly, some calcium channel blockers which are typically prescribed to patients with hypertension, coronary artery disease or arrhythmias have been shown to possibly have an impact on the response of bacterial biofilms to fluoroquinolones Elkhatib, Haynes and Noreddin , While the actual clinical significance of this novel form of drug—drug interaction remains to be discovered, it is intriguing that medications prescribed for other comorbid conditions could actually impact treatment outcomes with an antibiotic at the microbial level.

A screen for commonly prescribed medications with no inherent antimicrobial activity that either potentiate or antagonise a given antibiotic's ability to kill cells in a biofilm would be very useful in directing future research on how pharmaceuticals can influence antimicrobial resistance and tolerance in biofilms.

In summary, bacterial biofilms employ a multitude of mechanisms to survive antibiotic treatment. The importance of individual resistance and tolerance mechanisms varies depending on the antimicrobial agent in question and the growth conditions of the biofilm. By dissecting the complex, multifactorial nature of biofilm-specific antibiotic resistance and tolerance, we will be one step closer to improving clinical outcomes for patients suffering from chronic, treatment-refractory biofilm-based infections. Oxford University Press is a department of the University of Oxford.

It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Close mobile search navigation Article navigation. Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria Clayton W. Abstract Biofilms are surface-attached groups of microbial cells encased in an extracellular matrix that are significantly less susceptible to antimicrobial agents than non-adherent, planktonic cells.

View large Download slide. Antibiotics mentioned in this review and their major mechanisms of action. Some questions in biofilm-based antibiotic resistance and tolerance research. Mixed species biofilms of Candida albicans and Staphylococcus epidermidis. Phenotypes of non-attached Pseudomonas aeruginosa aggregates resemble surface attached biofilm.

Characterization of colony morphology variants isolated from Streptococcus pneumoniae biofilms. Formation of Streptococcus pneumoniae non-phase-variable colony variants is due to increased mutation frequency present under biofilm growth conditions. A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms.

Fitness landscape of antibiotic tolerance in Pseudomonas aeruginosa biofilms. Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Role of nutrient limitation and stationary-phase existence in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Cationic bactericidal peptide does not specifically target the stringnent response alarmone p ppGpp.

Increased emergence of fluoroquinolone-resistant Campylobacter jejuni in biofilm. Enhanced transmission of antibiotic resistance in Campylobacter jejuni biofilms by natural transformation. Rapid development in vitro and in vivo of resistance to ceftazidime in biofilm-growing Pseudomonas aeruginosa due to chromosomal beta-lactamase. Dynamics and spatial distribution of beta-lactamase expression in Pseudomonas aeruginosa biofilms.

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Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms. Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms. The biofilm-specific antibiotic resistance gene ndvB is important for expression of ethanol oxidation genes in Pseudomonas aeruginosa biofilms. Starvation, together with the SOS response, mediates high biofilm-specific tolerance to the fluoroquinolone ofloxacin.

Cross talk between the response regulators PhoB and TctD allows for the integration of diverse environmental signals in Pseudomonas aeruginosa. The extracellular matrix component Psl provides fast-acting antibiotic defense in Pseudomonas aeruginosa biofilms. Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Endogenous oxidative stress produces diversity and adaptability in biofilm communities.

Arginine or nitrate enhances antibiotic susceptbility of Pseudomonas aeruginosa in biofilms. Oxygen limitation contributes to antibiotic tolerance of Pseudomonas aeruginosa in biofilms. New insight into daptomycin bioavailability and localization in S. Mature Pseudomonas aeruginosa biofilms prevail compared to young biofilms in the presence of ceftazidime. The quorum sensing inhibitor hamamelitannin increases antibiotic susceptibility of Staphylococcus aureus biofilms by affecting peptidoglycan biosynthesis and eDNA release.

Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. Distinguishing between resistance, tolerance and persistence to antibiotic treatment. A dose-response study of antibiotic resistance in Pseudomonas aeruginosa biofilms. Resistance of bacterial biofilms to antibiotics: Interaction of Streptococcus pneumoniae and Moraxella catarrhalis: Pronlonged growth of a clinical Staphylococcus aureus strain selects for a stable small-colony variant cell type. Differential roles of RND efflux pumps in antimicrobial drug resistance of sessile and planktonic Burkholderia cenocepacia cells.

Genetic and biochemical analyses of the Pseudomonas aeruginosa Psl exopolysaccharide reveal overlapping roles for polysaccharide synthesis enzymes in Psl and LPS production. The Calgary Biofilm Device: Candida albicans ethanol stimulates Pseudomonas aeruginosa WspR-controlled biofilm formation as part of a cyclic relationship involving phenazines. Extracellular DNA shields against aminoglycosides in Pseudomonas aeruginosa biofilms. The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms.

Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms. Decreased susceptibility to antibiotic killing of a stable small colony variant of Staphylococcus aureus in fluid phase and on fibronectin-coated surfaces. PelA deacytlase activity is required for Pel polysacharride synthesis in Pseudomonas aeruginosa. The Pel polysaccharide can serve a structural and protective role in the biofilm matrix of Pseudomonas aeruginosa.

The Pel and Psl polysaccharides provide Pseudomonas aeruginosa structural redundancy within the biofilm matrix. Activated ClpP kills persisters and eradicates a chronic biofilm infection. Persister formation in Staphylococcus aureus is associated with ATP depletion. Effects of biofilm growth on plasmid copy number and expression of antibiotic resistance genes in Enterococcus faecalis. Bap, a Staphylococcus aureus surface protein involved in biofilm formation. Biofilms and their role in the resistance of pathogenic Candida to antifungal agents. Multiple roles for Enterococcus faecalis glycosyltransferases in biofilm-associated antibiotic resistance, cell envelope integrity, and conjugative transfer.

An in vivo polymicrobial biofilm wound infection model to study interspecies interactions. The GacS sensor kinase controls phenotypic reversion of small colony variants isolated from biofilms of Pseudomonas aeruginosa PA Broad-spectrum anti-biofilm peptide that targets a cellular stress response. D-enantiomeric peptides that eradicate wild-type and multidrug-resistant biofilms and protect against lethal Pseudomonas aeruginosa infections.

Extracellular DNA impedes the transport of vancomycin in Staphylococcus epidermidis biofilms preexposed to subinhibitory concentrations of vancomycin. The Pseudomonas aeruginosa transcriptome in planktonic cultures and static biofilms using RNA sequencing. Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Diffusion of rifampin and vancomycin through a Staphylococcus epidermidis biofilm. Antibiotics induce redox-related physiological alterations as part of their lethality. Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli.

Unexpected induction of resistant Pseudomonas aeruginosa biofilm to fluoroquinolones by diltiazem: Microbiological appraisal of levofloxacin activity against Pseudomonas aeruginosa biofilm in combination with different calcium chanel blockers in vitro. Bactericidal effects of antibiotics on slowly growing and nongrowing bacteria. Susceptibility of Pseudomonas aeruginosa and Escerichia coli biofilms towards ciprofloxacin: Alanine esters of enterococcal lipotechoic acid play a role in biofilm formation and resistance to antimicrobial peptides.

The bacterial type VI secretion machine: Oxidation of the guanine nucleotide pool underlies cell death by bactericidal antibiotics. Biosynthesis of the Pseudomonas aeruginosa extracellular polysaccharides, alginate, Pel, and Psl. Two genetic loci produce distinct carbohydrate-rich structural components of the Pseudomonas aeruginosa biofilm matrix. Antibiotic activity against small-colony variants of Staphylococcus aureus: The physiology and collective recalcitrance of microbial biofilm communities.

Molecular basis of azithromycin-resistant Pseudomonas aeruginosa biofilms.

Growing Resistance with Antibiotics [Book]

Induction of beta-lactamase production in Pseudomonas aeruginosa biofilm. Key role of techoic acid net charge in Staphylococcus aureus colonization of artificial surfaces. Elevated levels of the second messenger c-di-GMP contribute to antimicrobial resistance of Pseudomonas aeruginosa. Antimicrobial tolerance of Pseudomonas aeruginosa biofilms is activated during an early developmental stage and requires the two-component hybrid SagS.

Planktonic aggregates of Staphylococcus aureus protect against common antibiotics. Differentiation and distribution of colistin- and sodium dodecyl sulfate-tolerant cells in Pseudomonas aeruginosa biofilms. Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. Establishment of experimental biofilms using the Modified Robbins Device and flow cells. Candida albicans and Staphylococcus aureus form polymicrobial biofilms: Ability of Candida albicans mutants to induce Staphylococcus aureus vancomycin resistance during polymicrobial biofilm formation.

Importance of Candida -bacterial polymicrobial biofilms in disease. The use of microscopy and three-dimesional visualization to evaluate the structure of microbial biofilms cultivated in the Calgary Biofilm Device. Microtiter susceptibility testing of microbes growing on peg lids: The chromosomal toxin gene yafQ is a determinant of multidrug tolerance for Escherichia coli growing in a biofilm. Recent functional insights into the role of p ppGpp in bacterial physiology. High rates of conjugation in bacterial biofilms as determined by quantitative in situ analysis. Biofilm formation by the small colony variant phenotype of Pseudomonas aeruginosa.

Auto poisoning of the respiratory chain by a quorum-sensing-regulated molecule favors biofilm formation and antibiotic tolerance. RelA mutant Enterococcus faecium with multiantibiotic tolerance arising in an immunocompromised host. Calcium chelation by alginate activates the type III secretion system in mucoid Pseudomonas aeruginosa biofilms.

The molecular mechanisms and physiological consequences of oxidative stress: Increased antibiotic resistance of Escherichia coli in mature biofilms. Identification of psl , a locus encoding a potential exopolysaccharide that is essential for Pseudomonas aeruginosa PAO1 biofilm formation. Use of confocal microscopy to analyze the rate of vancomycin penetration through Staphylococcus aureus biofilms. Pel is a cationic exopolysaccharide that cross-links extracellular DNA in the Pseudomonas aeruginosa biofilm matrix.

Formation of hydroxyl radicals contributes to the bactericidal activity of ciprofloxacin against Pseudomonas aeruginosa biofilms. Extracellular DNA-induced antimicrobial peptide resistance in Salmonella enterica serovar Typhimurium. Surface-localized spermidine protects the Pseudomonas aeruginosa outer membrane from antibiotic treatment and oxidative stress.

Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli. Killing by bactericidal antibiotics does not depend on reactive oxygen species. The stringent response controls catalases in Pseudomonas aeruginosa and is required for hydrogen peroxide and antibiotic tolerance.

Aminoglycoside resistance of Pseudomonas aeruginosa biofilms modulated by extracellular polysaccharide. Bacterial persisters tolerate antibiotics by not producing hydroxyl radicals. Increased bactericidal activity of colistin on Pseudomonas aeruginosa biofilms in anaerobic conditions. Commensal protection of Staphylococcus aureus against antimicrobials by Candida albicans biofilm matrix. Increased transfer of a mutlidrug resistance plasmid in Escherichia coli biofilms at the air-liquid interface.

From in vitro to in vivo models of bacterial biofilm-related infections. Staphylococcus aureus persisters tolerant to bactericidal antibiotics.

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Extracellular DNA-induced antimicrobial peptide resistance mechanisms in Pseudomonas aeruginosa. The MerR-like transcriptional regulator BrlR contributes to Pseudomonas aeruginosa biofilm tolerance. The MerR-like regulator BrlR confers biofilm tolerance by activating multidrug efflux pumps in Pseudomonas aeruginosa biofilms. Cell death from antibiotics without the involvement of reactive oxygen species. Role of the rapA gene in controlling antibiotic resistance of Escherichia coli biofilms.

Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa. The interconnection between biofilm formation and horizontal gene transfer. A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance.

Antibiotic resisance in Pseudomonas aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system. High levels of genetic recombination during nasopharyngeal carriage and biofilm formation in Streptococcus pneumoniae. The fatty acid signaling molecule cis decenoic acid increases metabolic activity and reverts persister cells to an antimicrobial-susceptible state. A scanning and transmission electron microscopic study of an infected endocardial pacemaker lead.

Recent insights into Candida albicans biofilm resistance mechanisms. Putative exopolysaccharide synthesis genes influence Pseudomonas aeruginosa biofilm development. Association of CiaRH with resistance of Streptococcus mutans to antimicrobial peptides in biofilms. Pseudomonas aeruginosa as a cause of 1,3-beta-D-glucan assay reactivity.

Small colony variants have a major role in stability and persistence of Staphylococcus aureus biofilms. A role for sigma factor B in the emergence of Staphylococcus aureus small-colony variants and elevated biofilm production resulting from an exposure to aminoglycosides. Gene transfer occurs with enhanced efficiency in biofilms and induces enhanced stabilisation of the biofilm structure.

The developmental model of microbial biofilms: Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms. A well-plate-based optical method for the quantitative and qualitative evaluation of Pseudomonas aeruginosa biofilm formation and its application to susceptibility testing.

A continuum of anionic charge: Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Tobramycin resistance of Pseudomonas aeruginosa cells growing as a biofilm on urinary catheter material. The dlt genes play a role in antimicrobial tolerance of Streptococcus mutans biofilms. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB-oprM genes.

Reverting antibiotic tolerance of Pseudomonas aeruginosa PAO1 persister cells by Z bromo bromomethylene methylfuran-2 5H -one. A temporal examination of the planktonic and biofilm proteome of whole cell Pseudomonas aeruginosa PAO1 using quantitative mass spectrometry. Antimicrobial targets localize to the extracellular vesicle-associated proteome of Pseudomonas aeruginosa grown in a biofilm. Residence of Streptococcus pneumoniae and Moraxella catarrhalis within polymicrobial biofilm promotes antibiotic resistance and bacterial persistence in vivo.

The D-alanine residues of Staphylococcus aureus teichoic acids alter the susceptibility to vancomycin and the activity of autolytic enzymes. Staphylococcus aureus adherence to Candida albicans hyphae is mediated by the hyphal adhesin Als3p. SagS contributes to the motile-sessile switch and acts in concert with BfiSR to enable Pseudomonas aeruginosa biofilm formation.

Escaping the biofilm in more than one way: The novel Pseudomonas aeruginosa two-component regulator BfmR controls bacteriophage-mediated lysis and DNA-release during biofilm development through PhdA. Mannitol does not enhance tobramycin killing of Pseudomonas aeruginosa in a cystic fibrosis model system of biofilm formation.

Differential gene expression profiling of Staphylococcus aureus cultivated under biofilm and planktonic conditions. The biofilm life cycle and virulence of Pseudomonas aeruginosa are dependent on a filamentous phage.

Interspecies signalling via the Stenotrophomonas maltophilia diffusible signal factor influences biofilm formation and polymyxin tolerance in Pseudomonas aeruginosa. Increased mutability of Staphylococci in biofilms as a consequence of oxidative stress. High-level antibiotic resistance in Pseudomonas aeruginosa biofilm: Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm.

Staphylococcus aureus biofilms promote horizontal transfer of antibiotic resistance. The stringent response modulates 4-hydroxyalkylquinoline biosynthesis and quorum-sensing hierarchy in Pseudomonas aeruginosa.

What causes antibiotic resistance? - Kevin Wu

Published [Upper Saddle River, N. Other Authors Drlica, Karl. Subjects Drug resistance in microorganisms. Growing resistance with antibiotics. View online Borrow Buy Freely available Show 0 more links Other links Connect to this resource online at https: Set up My libraries How do I set up "My libraries"? This single location in All: Open to the public ; Online: Licence restrictions may apply Book English Show 0 more libraries