Salmonella enterica serovar Typhimurium multidrug efflux pumps EmrAB and AcrEF support the major efflux system AcrAB in decreased susceptibility to triclosan

Rensch, Ulrike; Nishino, Kunihiko; Klein, Günter; Kehrenberg, Corinna

doi:10.1016/j.ijantimicag.2014.04.015

Cited by 16 publications

(9 citation statements)

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“…ENR) resistance in Salmonella [ 40 , 41 ]. The efflux systems EmrAB and ArcEF have been shown to be important for both triclosan resistance [ 10 ] and trimethoprim resistance [ 42 ]. Our results support the previous observations of triclosan dependent increase of antibiotic resistance in different bacteria [ 43 – 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…Efflux pumps play a role in exporting toxic compounds from the cell and could be a common mechanism for antibiotic and biocide resistance [ 9 ]. The efflux systems EmrAB/AcrEF have been found to play a role in the susceptibility of Salmonella towards triclosan [ 10 ]. Furthermore, inactivation of the efflux pump genes acrB and tolC in Salmonella has previously been shown to decrease triclosan resistance [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Importance of sigma factor mutations in increased triclosan resistance in Salmonella Typhimurium

2015

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BackgroundSalmonella enterica is the second most common foodborne pathogen. The use of biocides is crucial to prevent spread of foodborne pathogens, and it would be devastating for food safety if Salmonella would become resistant to the disinfectants used. Another concern is that exposure to disinfectants might lead to decreased susceptibility to antibiotics.The current study aimed to identify genetic changes causing high level triclosan resistance in S. enterica serovar Typhimurium and evaluate how these affected antibiotic resistance and efflux pump activity.ResultsWild type strains S. Typhimurium 4/74 and DTU3 were adapted to increasing concentrations of the biocide triclosan by serial passage. High level triclosan resistant isolates (MIC > 1000 μg/ml) were obtained. Strains were genome sequenced, and SNPs in fabI, rpoS and rpoD were found to be associated with high level resistance. However, work with defined mutants revealed that a SNP in fabI was not sufficient to obtain high level resistance. This required additional mutations in the sigma factors rpoS or rpoD. The adapted strains showed triclosan-dependent increased efflux, increased fabI expression and reduced susceptibility towards the antibiotics enrofloxacin and sulphamethoxazole/trimethoprim.ConclusionsMedium level triclosan resistance could be obtained by fabI mutations in S. Typhimurium, however, high level resistance was found to require sigma factor mutations in addition to a fabI mutation. Reduced antibiotic sensitivity was observed for the adapted strains, which could be associated with increased efflux.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Importance of sigma factor mutations in increased triclosan resistance in Salmonella Typhimurium

2015

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“… 2014 ; Rensch et al. 2014 ; Gantzhorn, Olsen and Thomsen 2015 ). Therefore, caution should be used implementing such a strategy.…”

Section: Plasmid Curing Compoundsmentioning

confidence: 99%

Strategies to combat antimicrobial resistance: anti-plasmid and plasmid curing

Buckner

Ciusa

Piddock

2018

FEMS Microbiology Reviews

158

103

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Antimicrobial resistance (AMR) is a global problem hindering treatment of bacterial infections, rendering many aspects of modern medicine less effective. AMR genes (ARGs) are frequently located on plasmids, which are self-replicating elements of DNA. They are often transmissible between bacteria, and some have spread globally. Novel strategies to combat AMR are needed, and plasmid curing and anti-plasmid approaches could reduce ARG prevalence, and sensitise bacteria to antibiotics. We discuss the use of curing agents as laboratory tools including chemicals (e.g. detergents and intercalating agents), drugs used in medicine including ascorbic acid, psychotropic drugs (e.g. chlorpromazine), antibiotics (e.g. aminocoumarins, quinolones and rifampicin) and plant-derived compounds. Novel strategies are examined; these include conjugation inhibitors (e.g. TraE inhibitors, linoleic, oleic, 2-hexadecynoic and tanzawaic acids), systems designed around plasmid incompatibility, phages and CRISPR/Cas-based approaches. Currently, there is a general lack of in vivo curing options. This review highlights this important shortfall, which if filled could provide a promising mechanism to reduce ARG prevalence in humans and animals. Plasmid curing mechanisms which are not suitable for in vivo use could still prove important for reducing the global burden of AMR, as high levels of ARGs exist in the environment.

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“…The Salmonella EmrAB system confers resistance against novobiocin and nalidixic acid whereas it does not confer resistance to CCCP ( Figure 2 ) [ 185 ] . The EmrAB efflux pump is a multidrug efflux pump that can efflux substrates nalidixic acid, novobiocin and sodium deoxycholate from the bacterial cell [ 187 ]. Over-expression of the emrAB genes conferred resistance against novobiocin, nalidixic acid, rhodamine 6G and sodium deoxycholate (DOC) [ 185 ].…”

Section: Mechanisms Of Bacterial Drug Resistancementioning

confidence: 99%

Multidrug Efflux Pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus Bacterial Food Pathogens

Andersen

Kakarla

et al. 2015

IJERPH

131

106

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Foodborne illnesses caused by bacterial microorganisms are common worldwide and constitute a serious public health concern. In particular, microorganisms belonging to the Enterobacteriaceae and Vibrionaceae families of Gram-negative bacteria, and to the Staphylococcus genus of Gram-positive bacteria are important causative agents of food poisoning and infection in the gastrointestinal tract of humans. Recently, variants of these bacteria have developed resistance to medically important chemotherapeutic agents. Multidrug resistant Escherichia coli, Salmonella enterica, Vibrio cholerae, Enterobacter spp., and Staphylococcus aureus are becoming increasingly recalcitrant to clinical treatment in human patients. Of the various bacterial resistance mechanisms against antimicrobial agents, multidrug efflux pumps comprise a major cause of multiple drug resistance. These multidrug efflux pump systems reside in the biological membrane of the bacteria and actively extrude antimicrobial agents from bacterial cells. This review article summarizes the evolution of these bacterial drug efflux pump systems from a molecular biological standpoint and provides a framework for future work aimed at reducing the conditions that foster dissemination of these multidrug resistant causative agents through human populations.

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Salmonella enterica serovar Typhimurium multidrug efflux pumps EmrAB and AcrEF support the major efflux system AcrAB in decreased susceptibility to triclosan

Cited by 16 publications

References 5 publications

Importance of sigma factor mutations in increased triclosan resistance in Salmonella Typhimurium

Importance of sigma factor mutations in increased triclosan resistance in Salmonella Typhimurium

Strategies to combat antimicrobial resistance: anti-plasmid and plasmid curing

Multidrug Efflux Pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus Bacterial Food Pathogens

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