scholarly journals Conserved small protein associates with the multidrug efflux pump AcrB and differentially affects antibiotic resistance

2012 ◽  
Vol 109 (41) ◽  
pp. 16696-16701 ◽  
Author(s):  
E. C. Hobbs ◽  
X. Yin ◽  
B. J. Paul ◽  
J. L. Astarita ◽  
G. Storz
Keyword(s):  
Antibiotic Resistance ◽  
Efflux Pump ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Small Protein

scholarly journals Correlation between the Antibiotic Resistance Genes and Susceptibility to Antibiotics among the Carbapenem-Resistant Gram-Negative Pathogens

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 255
Author(s):  
Salma M. Abdelaziz ◽  
Khaled M. Aboshanab ◽  
Ibrahim S. Yahia ◽  
Mahmoud A. Yassien ◽  
Nadia A. Hassouna
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Efflux Pump ◽  
Antibiotic Resistance Genes ◽  
Multiple Drug ◽  
P Value ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Gram Negative ◽  
Carbapenem Resistant

In this study, the correlation between the antibiotic resistance genes and antibiotic susceptibility among the carbapenem-resistant Gram-negative pathogens (CRGNPs) recovered from patients diagnosed with acute pneumonia in Egypt was found. A total of 194 isolates including Klebsiella pneumoniae (89; 46%), Escherichia coli (47; 24%) and Pseudomonas aeruginosa (58; 30%) were recovered. Of these, 34 (18%) isolates were multiple drug resistant (MDR) and carbapenem resistant. For the K. pneumoniae MDR isolates (n = 22), blaNDM (14; 64%) was the most prevalent carbapenemase, followed by blaOXA-48 (11; 50%) and blaVIM (4; 18%). A significant association (p value < 0.05) was observed between the multidrug efflux pump (AcrA) and resistance to β-lactams and the aminoglycoside acetyl transferase gene (aac-6’-Ib) gene and resistance to ciprofloxacin, azithromycin and β-lactams (except for aztreonam). For P. aeruginosa, a significant association was noticed between the presence of the blaSHV gene and the multidrug efflux pump (MexA) and resistance to fluoroquinolones, amikacin, tobramycin, co-trimoxazole and β-lactams and between the aac-6’-Ib gene and resistance to aminoglycosides. All P. aeruginosa isolates (100%) harbored the MexAB-OprM multidrug efflux pump while 86% of the K. pneumoniae isolates harbored the AcrAB-TolC pump. Our results are of great medical importance for the guidance of healthcare practitioners for effective antibiotic prescription.

scholarly journals Multidrug Adaptive Resistance of Pseudomonas aeruginosa Swarming Cells

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Shannon R. Coleman ◽  
Travis Blimkie ◽  
Reza Falsafi ◽  
Robert E. W. Hancock
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Efflux Pump ◽  
Iron Acquisition ◽  
Polymyxin B ◽  
Rna Seq ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Content Type ◽  
Adaptive Resistance

ABSTRACT Swarming surface motility is a complex adaptation leading to multidrug antibiotic resistance and virulence factor production in Pseudomonas aeruginosa. Here, we expanded previous studies to demonstrate that under swarming conditions, P. aeruginosa PA14 is more resistant to multiple antibiotics, including aminoglycosides, β-lactams, chloramphenicol, ciprofloxacin, tetracycline, trimethoprim, and macrolides, than swimming cells, but is not more resistant to polymyxin B. We investigated the mechanism(s) of swarming-mediated antibiotic resistance by examining the transcriptomes of swarming cells and swarming cells treated with tobramycin by transcriptomics (RNA-Seq) and reverse transcriptase quantitative PCR (qRT-PCR). RNA-Seq of swarming cells (versus swimming) revealed 1,581 dysregulated genes, including 104 transcriptional regulators, two-component systems, and sigma factors, numerous upregulated virulence and iron acquisition factors, and downregulated ribosomal genes. Strain PA14 mutants in resistome genes that were dysregulated under swarming conditions were tested for their ability to swarm in the presence of tobramycin. In total, 41 mutants in genes dysregulated under swarming conditions were shown to be more resistant to tobramycin under swarming conditions, indicating that swarming-mediated tobramycin resistance was multideterminant. Focusing on two genes downregulated under swarming conditions, both prtN and wbpW mutants were more resistant to tobramycin, while the prtN mutant was additionally resistant to trimethoprim under swarming conditions; complementation of these mutants restored susceptibility. RNA-Seq of swarming cells treated with subinhibitory concentrations of tobramycin revealed the upregulation of the multidrug efflux pump MexXY and downregulation of virulence factors.

Characterization of the Serratia marcescens SdeCDE multidrug efflux pump studied via gene knockout mutagenesis

2008 ◽  
Vol 54 (5) ◽  
pp. 411-416 ◽  
Author(s):  
Sanela Begic ◽  
Elizabeth A. Worobec
Keyword(s):  
Antibiotic Resistance ◽  
Substrate Specificity ◽  
Serratia Marcescens ◽  
Efflux Pump ◽  
Gene Knockout ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Active Efflux ◽  
Major Mechanism

Serratia marcescens is an important nosocomial agent having high antibiotic resistance. A major mechanism for S. marcescens antibiotic resistance is active efflux. To ascertain the substrate specificity of the S. marcescens SdeCDE efflux pump, we constructed pump gene deletion mutants. sdeCDE knockout strains showed no change in antibiotic susceptibility in comparison with the parental strains for any of the substrates, with the exception of novobiocin. In addition, novobiocin was the only antibiotic to be accumulated by sdeCDE-deficient strains. Based on the substrates used in our study, we conclude that SdeCDE is a Resistance–Nodulation–Cell Division family pump with limited substrate specificity.

scholarly journals Metabolic Compensation of Fitness Costs Associated with Overexpression of the Multidrug Efflux Pump MexEF-OprN in Pseudomonas aeruginosa

2014 ◽  
Vol 58 (7) ◽  
pp. 3904-3913 ◽  
Author(s):  
Jorge Olivares ◽  
Carolina Álvarez-Ortega ◽  
José Luis Martinez
Keyword(s):  
Antibiotic Resistance ◽  
Respiratory Chain ◽  
Efflux Pump ◽  
Multidrug Efflux ◽  
Fitness Costs ◽  
Anaerobic Conditions ◽  
Multidrug Efflux Pump ◽  
Aerobic Conditions ◽  
Metabolic Compensation ◽  
Cytoplasmic Acidification

ABSTRACTThe acquisition of antibiotic resistance has been associated with a possible nonspecific, metabolic burden that is reflected in decreased fitness among resistant bacteria. We have recently demonstrated that overexpression of the MexEF-OprN multidrug efflux pump does not produce a metabolic burden when measured by classical competitions tests but rather leads to a number of changes in the organism's physiology. One of these changes is the untimely activation of the nitrate respiratory chain under aerobic conditions. MexEF-OprN is a proton/substrate antiporter. Overexpression of this element should result in a constant influx of protons, which may lead to cytoplasmic acidification. Acidification was not observed in aerobiosis, a situation in which the MexEF-overproducing mutant increases oxygen consumption. This enhanced oxygen uptake serves to eliminate intracellular proton accumulation, preventing the cytoplasmic acidification that was observed exclusively under anaerobic conditions, a situation in which the fitness of the MexEF-OprN-overproducing mutant decreases. Finally, we determined that the early activation of the nitrate respiratory chain under aerobic conditions plays a role in preventing a deleterious effect associated with the overexpression of MexEF-OprN. Our results show that metabolic rewiring may assist in overcoming the potential fitness cost associated with the acquisition of antibiotic resistance. Furthermore, the capability to metabolically compensate for this effect is habitat dependent, as demonstrated by our results under anaerobic conditions. The development of drugs that prevent metabolic compensation of fitness costs may help to reduce the persistence and dissemination of antibiotic resistance.

scholarly journals The thiol oxidation-based sensing and regulation mechanism for the OasR-mediated organic peroxide and antibiotic resistance in C. glutamicum

2020 ◽  
Vol 477 (19) ◽  
pp. 3709-3727
Author(s):  
Meiru Si ◽  
Can Chen ◽  
Chengchuan Che ◽  
Yang Liu ◽  
Xiaona Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antibiotic Resistance ◽  
Stress Response ◽  
Efflux Pump ◽  
Organic Peroxide ◽  
Antibiotics Resistance ◽  
Regulation Mechanism ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Redox Sensors

Corynebacterium glutamicum, an important industrial and model microorganism, inevitably encountered stress environment during fermentative process. Therefore, the ability of C. glutamicum to withstand stress and maintain the cellular redox balance was vital for cell survival and enhancing fermentation efficiency. To robustly survive, C. glutamicum has been equipped with many types of redox sensors. Although cysteine oxidation-based peroxide-sensing regulators have been well described in C. glutamicum, redox sensors involving in multiple environmental stress response remained elusive. Here, we reported an organic peroxide- and antibiotic-sensing MarR (multiple antibiotics resistance regulators)-type regulator, called OasR (organic peroxide- and antibiotic-sensing regulator). The OasR regulator used Cys95 oxidation to sense oxidative stress to form S-mycothiolated monomer or inter-molecular disulfide-containing dimer, resulting in its dissociation from the target DNA promoter. Transcriptomics uncovered the strong up-regulation of many multidrug efflux pump genes and organic peroxide stress-involving genes in oasR mutant, consistent with the phenomenon that oasR mutant showed a reduction in sensitivity to antibiotic and organic peroxide. Importantly, the addition of stress-associated ligands such as cumene hydroperoxide and streptomycin induced oasR and multidrug efflux pump protein NCgl1020 expression in vivo. We speculated that cell resistance to antibiotics and organic peroxide correlated with stress response-induced up-regulation of genes expression. Together, the results revealed that OasR was a key MarR-type redox stress-responsive transcriptional repressor, and sensed oxidative stress generated through hydroxyl radical formation to mediate antibiotic resistance in C. glutamicum.

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