Role of acid responsive genes in the susceptibility of Escherichia coli to ciclopirox

Shin, Jonghoon; Cho, Hyejin; Kim, Suran; Kim, Kwang-sun

doi:10.1016/j.bbrc.2018.04.063

Cited by 5 publications

(15 citation statements)

References 41 publications

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“…While we were preparing this work for publication, a study was published that concluded E . coli grown in 12.5 μg/mL of ciclopirox swarmed less and down-regulated the expression of 4/5 motility-associated genes [29]. At 10 μg/mL ciclopirox, our highest tested concentration, we also saw decreased swarming for this K12 laboratory strain.…”

Section: Resultsmentioning

confidence: 66%

“…coli also double in size during swarming, thereby doubling the number of flagella per cell [82]. The average BW25113 strain cell length increases from 2.8 to 3.4 μM when treated with 12.5 μg/mL ciclopirox [29]. At this ciclopirox concentration, however, BW25113 swarming decreases [29].…”

Section: Discussionmentioning

confidence: 99%

“…The average BW25113 strain cell length increases from 2.8 to 3.4 μM when treated with 12.5 μg/mL ciclopirox [29]. At this ciclopirox concentration, however, BW25113 swarming decreases [29].…”

Section: Discussionmentioning

confidence: 99%

“…coli strain grown with sublethal concentrations of ciclopirox. In that work, they identified 514 differentially expressed genes, including 123 involved in metabolite transport and down-regulation of an Rcs protein gene ( rcsD) [29]. They also identified the involvement of glutamate-dependent acid resistance genes and the global transcriptional silencer encoded by the gene hns in ciclopirox susceptibility in E .…”

Section: Discussionmentioning

confidence: 99%

“…The excellent safety profile and lack of fungal resistance also make ciclopirox a prime candidate for repurposing as an antibacterial agent [27–29]. Ciclopirox blocks growth of A .…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Sugar and iron: Toward understanding the antibacterial effect of ciclopirox in Escherichia coli

Conley¹,

Carlson-Banning²,

Carter³

et al. 2019

PLoS ONE

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New antibiotics are needed against antibiotic-resistant gram-negative bacteria. The repurposed antifungal drug, ciclopirox, equally blocks antibiotic-susceptible or multidrug-resistant Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae clinical isolates, indicating that it is not affected by existing resistance mechanisms. Toward understanding how ciclopirox blocks growth, we screened E. coli mutant strains and found that disruption of genes encoding products involved in galactose salvage, enterobacterial common antigen synthesis, and transport of the iron binding siderophore, enterobactin, lowered the minimum inhibitory concentration of ciclopirox needed to block growth of the mutant compared to the isogenic parent strain. We found that ciclopirox induced enterobactin production and that this effect is strongly affected by the deletion of the galactose salvage genes encoding UDP-galactose 4-epimerase, galE, or galactose-1-phosphate uridylyltransferase, galT. As disruption of ECA synthesis activates the regulation of capsular synthesis (Rcs) phosphorelay, which inhibits bacterial swarming and promotes biofilm development, we test whether ciclopirox prevents activation of the Rcs pathway. Sub-inhibitory concentrations of ciclopirox increased swarming of the E. coli laboratory K12 strain BW25113 but had widely varying effects on swarming or surface motility of clinical isolate E. coli, A. baumannii, and K. pneumoniae. There was no effect of ciclopirox on biofilm production, suggesting it does not target Rcs. Altogether, our data suggest ciclopirox-mediated alteration of lipopolysaccharides stimulates enterobactin production and affects bacterial swarming.

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Section: Resultsmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The excellent safety profile and lack of fungal resistance also make ciclopirox a prime candidate for repurposing as an antibacterial agent [27–29]. Ciclopirox blocks growth of A .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Sugar and iron: Toward understanding the antibacterial effect of ciclopirox in Escherichia coli

Conley¹,

Carlson-Banning²,

Carter³

et al. 2019

PLoS ONE

View full text Add to dashboard Cite

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Plastic wastes and surface antibiotic resistance genes pollution in mangrove environments

Sun

Liu

et al. 2023

Environ Monit Assess

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Modelling the metabolic consequences of antimicrobial exposure

Alonso-Vásquez

Riccardi

Passeri

et al. 2022

Preprint

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Besides genetic mutations, the metabolic state of bacterial cells represents another driving factor in the emergence of antimicrobial resistance and in the actual efficacy of treatments. In this direction, studying how bacteria reprogram their metabolism when facing antimicrobial exposure is crucial to enhance our ability to limit the development and spread of antibiotic resistance. Here we have studied the metabolic consequences of antimicrobial exposure in bacteria using an integrated approach that exploits transcriptomics and computational modelling. Specifically, we asked whether common metabolic strategies emerge during the exposure to antimicrobials, regardless of the kind of antimicrobial used or, on the contrary, antimicrobial-specific pathways exist. To this purpose, we have used an heterogeneous dataset from six published studies on Escherichia coli exposed to different concentrations/types of compounds. We show that experimental condition, not antimicrobial exposure, is the factor that influences the most the resulting metabolic networks. However, despite condition-dependent metabolic signatures being evident, specific changes in flux distributions by antimicrobial exposed cells could be identified. In particular, purine and pyrimidine biosynthesis, and cofactor and prosthetic group biosynthesis were commonly affected by all considered antimicrobials. This suggests the presence of general metabolic strategies to face the stress posed by antimicrobial exposure and that, in turn, may represent an untapped resource for the fight against microbial infections. Finally, our analysis predicted an overall metabolic rewiring following bacteriostatic vs. bactericidal drug exposure that is in line with the current knowledge about the effects of these two classes of compounds on microbial metabolic phenotypes.

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Role of acid responsive genes in the susceptibility of Escherichia coli to ciclopirox

Cited by 5 publications

References 41 publications

Sugar and iron: Toward understanding the antibacterial effect of ciclopirox in Escherichia coli

Sugar and iron: Toward understanding the antibacterial effect of ciclopirox in Escherichia coli

Plastic wastes and surface antibiotic resistance genes pollution in mangrove environments

Modelling the metabolic consequences of antimicrobial exposure

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