Efflux Impacts Intracellular Accumulation Only in Actively Growing Bacterial Cells

Whittle, Emily E; McNeil, Helen E; Trampari, Eleftheria; Webber, Mark A.; Overton, Tim W.; Blair, Jessica M A

doi:10.1128/mbio.02608-21

Cited by 20 publications

(22 citation statements)

References 51 publications

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“…The resulting parameters suggest early rapid accumulation of the substrate followed by a decrease in cell permeability. This compares favourably against more recent experimental data that demonstrate that changes in substrate accumulation in later growth are dominated by changes in permeability rather than efflux [43].…”

Section: Quantifying Effluxsupporting

confidence: 75%

Unravelling microbial efflux through mathematical modelling

Jabbari

2022

Microbiology

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Mathematical modelling is a useful tool that is increasingly used in the life sciences to understand and predict the behaviour of biological systems. This review looks at how this interdisciplinary approach has advanced our understanding of microbial efflux, the process by which microbes expel harmful substances. The discussion is largely in the context of antimicrobial resistance, but applications in synthetic biology are also touched upon. The goal of this paper is to spark further fruitful collaborations between modellers and experimentalists in the efflux community and beyond.

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Section: Quantifying Effluxsupporting

confidence: 75%

Unravelling microbial efflux through mathematical modelling

Jabbari

2022

Microbiology

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“…Supporting this, deletion of dskA in E. coli resulted in a significant increase in acriflavine susceptibility (), however previous work found no significant difference in efflux activity following deletion of rpoS in S. Typhimurium [39]. These genes may affect efflux regulation through marR , whose expression has been reported to increase (resulting in repression of marA ) following deletion of either dksA [40] or rpoS [41].…”

Section: Resultsmentioning

confidence: 94%

Genome-wide analysis of genes involved in efflux function and regulation within Escherichia coli and Salmonella enterica serovar Typhimurium

et al. 2023

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The incidence of multidrug-resistant bacteria is increasing globally, with efflux pumps being a fundamental platform limiting drug access and synergizing with other mechanisms of resistance. Increased expression of efflux pumps is a key feature of most cells that are resistant to multiple antibiotics. Whilst expression of efflux genes can confer benefits, production of complex efflux systems is energetically costly and the expression of efflux is highly regulated, with cells balancing benefits against costs. This study used TraDIS-Xpress, a genome-wide transposon mutagenesis technology, to identify genes in Escherichia coli and Salmonella Typhimurium involved in drug efflux and its regulation. We exposed mutant libraries to the canonical efflux substrate acriflavine in the presence and absence of the efflux inhibitor phenylalanine-arginine β-naphthylamide. Comparisons between conditions identified efflux-specific and drug-specific responses. Known efflux-associated genes were easily identified, including acrAB, tolC, marRA, ramRA and soxRS, confirming the specificity of the response. Further genes encoding cell envelope maintenance enzymes and products involved with stringent response activation, DNA housekeeping, respiration and glutathione biosynthesis were also identified as affecting efflux activity in both species. This demonstrates the deep relationship between efflux regulation and other cellular regulatory networks. We identified a conserved set of pathways crucial for efflux activity in these experimental conditions, which expands the list of genes known to impact on efflux efficacy. Responses in both species were similar and we propose that these common results represent a core set of genes likely to be relevant to efflux control across the Enterobacteriaceae.

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“…In the study of Whittle et al (2021) , the authors showed that there was no significant difference in EtBr accumulation when measuring it in single cells, at different growth phases. Only one case was different, when efflux deficient strains were used.…”

Section: Discussionmentioning

confidence: 99%

Estimating the optimal efflux inhibitor concentration of carvacrol as a function of the bacterial physiological state

et al. 2023

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Our aim was to find the optimal efflux inhibitor concentration of a natural component, carvacrol, as a function of the physiological state of Escherichia coli. Using fluorescence-based measurements with two strains of E. coli, the effect of carvacrol was assessed at 17 sub-inhibitory concentrations, at which the bacterial efflux mechanism was compromised. The efficacy of carvacrol, as an efflux inhibitor, was compared to synthetic inhibitors and we found carvacrol the most efficient one. We considered the accumulation of Ethidium Bromide (EtBr) as a proxy for drugs spreading in the cell, thus measuring the efflux activity indirectly. The change in membrane integrity caused by the exposure to carvacrol was monitored using the LIVE/DEAD BacLight Bacterial Viability kit. To find the optimal inhibitory concentration of carvacrol, we used predictive microbiology methods. This optimum varied with the bacterial physiological state, as non-growing cultures were less susceptible to the effect of carvacrol than growing cultures were. Moreover, we point out, for the first time, that the efflux-mediated resistance of untreated cultures was also stronger in the non-growing than in the growing phase at population level.

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Efflux Impacts Intracellular Accumulation Only in Actively Growing Bacterial Cells

Cited by 20 publications

References 51 publications

Unravelling microbial efflux through mathematical modelling

Unravelling microbial efflux through mathematical modelling

Genome-wide analysis of genes involved in efflux function and regulation within Escherichia coli and Salmonella enterica serovar Typhimurium

Estimating the optimal efflux inhibitor concentration of carvacrol as a function of the bacterial physiological state

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