scholarly journals Resistance in Staphylococcus Aureus: The Never-Ending Story

2016 ◽  
Vol 33 (3) ◽  
pp. 153-162
Author(s):  
Jovan Orlović ◽  
Biljana Miljković-Selimović ◽  
Marina Dinić ◽  
Ljiljana Ristić
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Mechanisms Of Resistance ◽  
Antibacterial Drugs ◽  
Ongoing Effort ◽  
Growth And Reproduction

Summary Combating Staphylococcus aureus (S. aureus) infections using antibacterial drugs is actually an ongoing effort to overcome resistance mechanism of this microorganism. In this paper, we discussed (1) the mechanisms of resistance to some of the most commonly used antimicrobial agents in the treatment of S. aureus: methicillin, vancomicyn and quinolones. In addition, (2) efflux pump mechanisms involved in maintaining homeostasis in the presence of compounds that inhibit S. aureus growth and reproduction, as well as mechanisms of resistance to a number of antibiotics, have been reviewed.

scholarly journals Efflux-Related Resistance to Norfloxacin, Dyes, and Biocides in Bloodstream Isolates of Staphylococcus aureus

2007 ◽  
Vol 51 (9) ◽  
pp. 3235-3239 ◽  
Author(s):  
Carmen E. DeMarco ◽  
Laurel A. Cushing ◽  
Emmanuel Frempong-Manso ◽  
Susan M. Seo ◽  
Tinevimbo A. A. Jaravaza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Efflux Pump Inhibitor ◽  
Qrt Pcr ◽  
Reverse Transcription Pcr ◽  
Environmental Surfaces ◽  
Genes Encoding ◽  
High Level

ABSTRACT Efflux is an important resistance mechanism in Staphylococcus aureus, but its frequency in patients with bacteremia is unknown. Nonreplicate bloodstream isolates were collected over an 8-month period, and MICs of four common efflux pump substrates, with and without the broad-spectrum efflux pump inhibitor reserpine, were determined (n = 232). A reserpine-associated fourfold decrease in MIC was considered indicative of efflux. Strains exhibiting efflux of at least two of the four substrates were identified (“effluxing strains” [n = 114]). For these strains, MICs with or without reserpine for an array of typical substrates and the expression of mepA, mdeA, norA, norB, norC, and qacA/B were determined using quantitative real-time reverse transcription-PCR (qRT-PCR). A fourfold or greater increase in gene expression was considered significant. The most commonly effluxed substrates were ethidium bromide and chlorhexidine (100 and 96% of effluxing strains, respectively). qRT-PCR identified strains overexpressing mepA (5 [4.4%]), mdeA (13 [11.4%]), norA (26 [22.8%]), norB (29 [25.4%]), and norC (19 [16.7%]); 23 strains overexpressed two or more genes. Mutations probably associated with increased gene expression included a MepR-inactivating substitution and norA promoter region insertions or deletions. Mutations possibly associated with increased expression of the other analyzed genes were also observed. Effluxing strains comprised 49% of all strains studied (114/232 strains), with nearly half of these overexpressing genes encoding MepA, MdeA, and/or NorABC (54/114 strains). Reduced susceptibility to biocides may contribute to persistence on environmental surfaces, and efflux of drugs such as fluoroquinolones may predispose strains to high-level target-based resistance.

Carbapenem-resistantAcinetobacter baumannii: diversity of resistant mechanisms and risk factors for infection

2011 ◽  
Vol 140 (1) ◽  
pp. 137-145 ◽  
Author(s):  
Y. J. KIM ◽  
S. I. KIM ◽  
Y. R. KIM ◽  
K. W. HONG ◽  
S. H. WIE ◽  
...  
Keyword(s):  
Risk Factors ◽  
Efflux Pump ◽  
Clinical Epidemiology ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Apache Ii Score ◽  
Mechanisms Of Resistance ◽  
High Apache ◽  
Carbapenem Resistant ◽  
Clonal Spread

SUMMARYCarbapenem-resistantAcinetobacter baumannii(CRAB) are an increasing infectious threat in hospitals. We investigated the clinical epidemiology of CRAB infectionsvs. colonization in patients, and examined the mechanisms of resistance associated with elevated minimum inhibitory concentrations (MICs) for carbapenems. From January to June 2009, 75 CRAB strains were collected. CRAB infection was significantly associated with malignancy and a high APACHE II score. The most dominant resistance mechanism was ISAba1preceding OXA-51, producing strains with overexpression of efflux pump. Strains carryingblaOXA-23-like enzymes had higher carbapenem MICs than those carryingblaOXA-51-like enzymes; however, the presence of multiple mechanisms did not result in increased resistance to carbapenems. There was no difference in the resistance mechanisms in strains from infected and colonized patients. The majority of strains were genetically diverse by DNA macrorestriction although there was evidence of clonal spread of four clusters of strains in patients.

scholarly journals Effect of MexXY Overexpression on Ceftobiprole Susceptibility in Pseudomonas aeruginosa

2009 ◽  
Vol 53 (7) ◽  
pp. 2785-2790 ◽  
Author(s):  
Ellen Z. Baum ◽  
Steven M. Crespo-Carbone ◽  
Brian J. Morrow ◽  
Todd A. Davies ◽  
Barbara D. Foleno ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Broad Spectrum ◽  
Efflux Pump ◽  
Regulatory Gene ◽  
Resistance Mechanism ◽  
Common Mechanism ◽  
Spontaneous Mutant ◽  
Minimal Effect ◽  
Strain Pao1

ABSTRACT Ceftobiprole, an anti-methicillin-resistant Staphylococcus aureus broad-spectrum cephalosporin, has activity (MIC for 50% of strains tested, ≤4 μg/ml) against many Pseudomonas aeruginosa strains. A common mechanism of P. aeruginosa resistance to β-lactams, including cefepime and ceftazidime, is efflux via increased expression of Mex pumps, especially MexAB. MexXY has differential substrate specificity, recognizing cefepime but not ceftazidime. In ceftobiprole clinical studies, paired isolates of P. aeruginosa from four subjects demonstrated ceftobiprole MICs of 2 to 4 μg/ml at baseline but 16 μg/ml posttreatment, unrelated to β-lactamase levels. Within each pair, the level of mexXY RNA, but not mexAB, mexCD, and mexEF, increased by an average of 50-fold from baseline to posttreatment isolates. Sequencing of the negative regulatory gene mexZ indicated that each posttreatment isolate contained a mutation not present at baseline. mexXY expression as a primary ceftobiprole and cefepime resistance mechanism was further examined in isogenic pairs by using cloned mexXY and mexZ. Expression of cloned mexXY in strain PAO1 or in a baseline isolate increased the ceftobiprole MIC to that for the posttreatment isolate. In contrast, in posttreatment isolates, lowering mexXY expression via introduction of cloned mexZ decreased the ceftobiprole MIC to that for the baseline isolates. Similar changes were observed for cefepime. A spontaneous mutant selectively overexpressing mexXY displayed a fourfold elevation in its ceftobiprole MIC, while overexpression of mexAB, -CD, and -EF had a minimal effect. These data indicate that ceftobiprole, like cefepime, is an atypical β-lactam that is a substrate for the MexXY efflux pump in P. aeruginosa.

The Expression of Efflux Pump Genes in Methicillin-Resistant Staphylococcus aureus (MRSA) Strains Isolated from Blood Cultures in Iran

2020 ◽  
Vol 15 (5) ◽  
Author(s):  
Arezoo Bostanmaneshrad ◽  
Jamileh Norouzi ◽  
Gita Eslami ◽  
Ali Hashemi
Keyword(s):  
Staphylococcus Aureus ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Expression Level ◽  
Resistance Pattern ◽  
Dilution Method ◽  
University Hospitals ◽  
Efflux Pump Inhibitor ◽  
Disk Diffusion Test ◽  
Methicillin Resistant

Background: Efflux pump is a significant resistance mechanism in Staphylococcus aureus. A total of 100 patients with bacteremia from Shahid Beheshti University Hospitals of Tehran in Iran were tested for the expression of efflux pump genes, contributing to S. aureus antimicrobial resistance. Objectives: this study was conducted to identify resistance pattern, and to evaluate the inhibitory effect of efflux pump, MIC of ciprofloxacin, and expression levels of norA, norB, and norC efflux pump genes in the presence of an efflux pump inhibitor against MDR S. aureus. Methods: A total of 100 MRSA isolates were investigated in different hospitals of Shahid Beheshti University of Medical Sciences from April 2017-2018. Owing to new consensus guidelines from the Clinical and Laboratory Standards Institute (CLSI), both the Kirby-Bauer disk diffusion test and micro-dilution method were used to evaluate antimicrobial susceptibility. Efflux pump activity using carbonyl cyanide 3-chlorophenylhydrazone (CCCP) was identified as a chemical efflux pump inhibitor. E-test was used to determine Vancomycin-resistant antibiotic. Broth micro-dilution method for S. aureus isolates resistant to ciprofloxacin has been developed for minimum inhibitory concentration (MIC) of ciprofloxacin and CCCP and their composition. Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) was used to investigate the expression level of norA, norB, and norC efflux pump genes. Results: A total of 38 of 45 MRSA isolates (84.4%) showed resistance to ciprofloxacin. Moreover, 100% of isolates had the norA and norB genes. Further, 95% of S. aureus isolates had the norC gene. According to this study, ciprofloxacin MIC has decreased by CCCP compared to ciprofloxacin. There was an increase in the expression level of norA, norB, and norC efflux pump genes in methicillin-resistant and ciprofloxacin-resistant S. aureus strains based on RT- PCR. In this study, four different spA types were obtained as the most prevalent type of spA by t037and t790 (23.3%) and t030 (14.1%) and t044 (12.2%). Conclusions: This study indicates that the prevalence of ciprofloxacin-resistant S. aureus strains has a rising trend among MRSA clinical isolates. The ability of S. aureus isolates to be converted into drug-resistant strains using efflux pump mechanism has become a widespread concern.

scholarly journals Mechanisms of Resistance to Daptomycin in Enterococcus faecium

2008 ◽  
Vol 52 (3) ◽  
pp. 1167-1170 ◽  
Author(s):  
Clemente I. Montero ◽  
Frida Stock ◽  
Patrick R. Murray
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecium ◽  
Soil Bacteria ◽  
Leukocyte Adhesion ◽  
Resistance Mechanism ◽  
Point Mutations ◽  
Deficiency Syndrome ◽  
Leukocyte Adhesion Deficiency ◽  
Mechanisms Of Resistance ◽  
Equivalent Point

ABSTRACT In this study, we investigated the clonal emergence of daptomycin-resistant Enterococcus faecium strains isolated from a patient with leukocyte adhesion deficiency syndrome. The resistance mechanism in these strains is independent of either equivalent point mutations previously described for Staphylococcus aureus or daptomycin inactivation mechanisms identified in soil bacteria.

scholarly journals Mechanisms of Resistance to Quinolones and Epidemiological Significance of Salmonella spp.

2016 ◽  
Vol 66 (2) ◽  
pp. 147-159 ◽  
Author(s):  
Maja Velhner
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Quinolone Resistance ◽  
Beta Lactam ◽  
Foodborne Illnesses ◽  
Salmonella Spp ◽  
Over Expression ◽  
Beta Lactam Antibiotics ◽  
Chromosomal Mutations

Abstract Bacteria develop resistance to antimicrobial agents by a number of different mechanisms. The resistance to (fluoro)quinolones in Salmonella is of particular importance especially if therapy in humans is required. For decades there has been a significant interest in studying the biology of Salmonella because these bacteria are among the leading causes of foodborne illnesses around the globe. To this date, two main mechanisms of quinolone resistance have been established: alteration in the targets for quinolones, decreased accumulation inside bacteria due to impermeability of the membrane and/or an over expression of the efflux pump systems. Both of these mechanisms are chromosomally mediated. Furthermore, mobile elements have been described carrying the qnr gene which confers resistance to quinolones. The plasmid encoded QNR proteins belong to the pentapeptide repeat family of proteins. The plasmid mediated quinolone resistance (PMQR) is often associated with the resistance to beta lactam antibiotics. It was noticed that PMQR is backing up chromosomal mutations for quinolone resistance, hence becoming an important resistance mechanism worldwide. Even with our knowledge expanding over the years, it is not possible to predict how bacteria will respond in the future, if they are exposed to new external challenges. The possibility that they will find a way to survive by introducing new mutations or by exchanging mobile genetic elements and subsequently developing resistance to survive in the environment should not be underestimated.

scholarly journals Phenothiazines and Thioxanthenes Inhibit Multidrug Efflux Pump Activity in Staphylococcus aureus

2003 ◽  
Vol 47 (2) ◽  
pp. 719-726 ◽  
Author(s):  
Glenn W. Kaatz ◽  
Varsha V. Moudgal ◽  
Susan M. Seo ◽  
Jette E. Kristiansen
Keyword(s):  
Staphylococcus Aureus ◽  
Transmembrane Potential ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Sequencing Data ◽  
Multidrug Efflux ◽  
Inhibitory Effects ◽  
Multidrug Efflux Pump ◽  
Synergistic Interactions ◽  
Pump Activity

ABSTRACT Efflux-related multidrug resistance (MDR) is a significant means by which bacteria can evade the effects of selected antimicrobial agents. Genome sequencing data suggest that Staphylococcus aureus may possess numerous chromosomally encoded MDR efflux pumps, most of which have not been characterized. Inhibition of these pumps, which may restore clinically relevant activity of antimicrobial agents that are substrates for them, may be an effective alternative to the search for new antimicrobial agents that are not substrates. The inhibitory effects of selected phenothiazines and two geometric stereoisomers of the thioxanthene flupentixol were studied using strains of S. aureus possessing unique efflux-related MDR phenotypes. These compounds had some intrinsic antimicrobial activity and, when combined with common MDR efflux pump substrates, resulted in additive or synergistic interactions. For S. aureus SA-1199B, which overexpresses the NorA MDR efflux pump, and for two additional strains of S. aureus having non-NorA-mediated MDR phenotypes, the 50% inhibitory concentration (IC50) for ethidium efflux for all tested compounds was between 4 and 15% of their respective MICs. Transport of other substrates was less susceptible to inhibition; the prochlorperazine IC50 for acriflavine and pyronin Y efflux by SA-1199B was more than 60% of its MIC. Prochlorperazine and trans(E)-flupentixol were found to reduce the proton motive force (PMF) of S. aureus by way of a reduction in the transmembrane potential. We conclude that the mechanism by which phenothiazines and thioxanthenes inhibit efflux by PMF-dependent pumps is multifactorial and, because of the unbalanced effect of these compounds on the MICs and the efflux of different substrates, may involve an interaction with the pump itself and, to a lesser extent, a reduction in the transmembrane potential.

Antistaphylococcal activity of carbonic acid extract of hops

2018 ◽  
Vol 22 (2) ◽  
pp. 297-300
Author(s):  
V.V. Nevmerzhitsky ◽  
V.Yu. Ivannik ◽  
V.V. Kazmirchuk ◽  
T.N. Moiseenko ◽  
T.A. Volkov ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Antimicrobial Agents ◽  
Carbonic Acid ◽  
Inflammatory Diseases ◽  
Acquired Resistance ◽  
Biologically Active ◽  
Antibacterial Drugs ◽  
Antistaphylococcal Activity ◽  
Prevention And Treatment ◽  
Main Disadvantage

The fight against staphylococcal infection, increasing the effectiveness of methods of prevention and treatment of diseases of staphylococcal etiology is of interest to scientists and practitioners, both in Ukraine and around the world. The urgency of this problem is growing rapidly, as there is a tendency to increase the resistance of not only staphylococci, but also other gram-positive bacteria. The spread of methicillin-resistant staphylococci restricts the choice of antibiotics for the treatment of diseases of staphylococcal etiology. Staphylococcus aureus is the most common and dangerous type, which is one of the main factors of purulent-inflammatory lesions of the skin and mucous membranes. As a result of mutations, pathogenic staphylococci acquired resistance to antibacterial drugs. The main disadvantage of modern antibiotics is their non-selectivity. As a result of mutations, pathogenic staphylococci acquired resistance to antibacterial drugs. The main disadvantage of modern antibiotics is their non-selectivity. One of the unique and promising medicinal plants, which contains a rich complex of biologically active substances (BAS), is common hops (Humulus lupulus L.). The complex of BAS (flavonoids, hormones, vitamins, bitter, phenolic compounds, essential oils) causes anti-inflammatory, bactericidal, hyposensitizing and analgesic action of hops. The purpose of this work is to determine the antistaphylococcal activity of the carbon dioxide extract of hops and to justify the development on its basis of new antimicrobial agents for the prevention and treatment of infectious and purulent-inflammatory diseases. The following methods were used: microbiological (method of diffusion into agar (well method)) and mathematical and statistical. The high antimicrobial activity of the carbon dioxide extract of hops has been established for museum test strains of the genus Staphylococcus. The results of the studies testify to the prospects of further study of the bactericidal properties of the extract of hops carbon dioxide with the aim of creating effective antimicrobial agents on its basis for the prevention and treatment of infectious and purulent-inflammatory diseases of staphylococcal etiology.

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