ArticleThe Journal of biological chemistry2014
The CpxR/CpxA two-component regulatory system up-regulates the multidrug resistance cascade to facilitate Escherichia coli resistance to a model antimicrobial peptide.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 126 citations in OpenAlex.
- Indole decreases the virulence of enterotoxigenic Escherichia coli.World journal of microbiology & biotechnology · 2026Article
- AResKGLM: a graph-grounded language-model framework for interpretable multi-hop antimicrobial resistance reasoning.Briefings in bioinformatics · 2026Article
- Whole-Genome Analysis of Multidrug-Resistant Escherichia coli from Bloodstream Infections in Iraqi Cancer Patients.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- ThemBio · 2026Article
- Antimicrobial Peptides Against Antimicrobial-Resistant Bacteria: Focus on Machine Learning.Infection and drug resistance · 2026Review
- CpxR and LrhA coordinate the regulation of Xenocoumacin 1 biosynthesis, flagellar assembly, and chemotaxis inFrontiers in microbiology · 2026Article
- Heterogeneous efflux pump expression underpins phenotypic resistance to antimicrobial peptides.eLife · 2025Article
- A Designed ZnJournal of the American Chemical Society · 2025Article
- Lacritin cleavage-potentiated targeting of iron - respiratory reciprocity promotes bacterial death.The Journal of biological chemistry · 2025Article
- Genome-Wide Screens Identify Genes Responsible for Intrinsic Boric Acid Resistance in Escherichia coli.Biological trace element research · 2024Article
- Breaking Barriers: Exploiting Envelope Biogenesis and Stress Responses to Develop Novel Antimicrobial Strategies in Gram-Negative Bacteria.Pathogens (Basel, Switzerland) · 2024Review
- Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review.Microorganisms · 2024Review
- The CpxRA two-component system of adherent and invasiveInfection and immunity · 2024Article
- Roles of DJ41_1407 and DJ41_1408 inInternational journal of molecular sciences · 2024Article
- Article
- Cpx-signalling innpj antimicrobials and resistance · 2024Article
- Long-term exposure to food-grade disinfectants causes cross-resistance to antibiotics in Salmonella enterica serovar Typhimurium strains with different antibiograms and sequence types.Antimicrobial resistance and infection control · 2023Article
- Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response.BMC biology · 2023Article
- Pseudomonas aeruginosa Resists Phage Infection via Eavesdropping on Indole Signaling.Microbiology spectrum · 2023Article
- Genome-wide analysis of genes involved in efflux function and regulation withinMicrobiology (Reading, England) · 2023Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
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Abstract
A genome-wide susceptibility assay was used to identify specific CpxR-dependent genes that facilitate Escherichia coli resistance to a model cationic antimicrobial peptide, protamine. A total of 115 strains from the Keio Collection, each of which contained a deletion at a demonstrated or predicted CpxR/CpxA-dependent locus, were tested for protamine susceptibility. One strain that exhibited high susceptibility carried a deletion of tolC, a gene that encodes the outer membrane component of multiple tripartite multidrug transporters. Concomitantly, two of these efflux systems, AcrAB/TolC and EmrAB/TolC, play major roles in protamine resistance. Activation of the CpxR/CpxA system stimulates mar transcription, suggesting a new regulatory circuit that enhances the multidrug resistance cascade. Tripartite multidrug efflux systems contribute to bacterial resistance to protamine differently from the Tat system. DNase I footprinting analysis demonstrated that the CpxR protein binds to a sequence located in the -35 and -10 regions of mar promoter. This sequence resembles the consensus CpxR binding site, however, on the opposite strand. aroK, a CpxR-dependent gene that encodes a shikimate kinase in the tryptophan biosynthesis pathway, was also found to facilitate protamine resistance. Specific aromatic metabolites from this pathway, such as indole, can stimulate expression of well studied CpxR-dependent genes degP and cpxP, which are not components of the tripartite multidrug transporters. Thus, we propose a novel mechanism for E. coli to modulate resistance to protamine and likely other cationic antimicrobial peptides in which the CpxR/CpxA system up-regulates mar transcription in response to specific aromatic metabolites, subsequently stimulating the multidrug resistance cascade.
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