ArticleJournal of bacteriology2014
Role of the CpxAR two-component signal transduction system in control of fosfomycin resistance and carbon substrate uptake.
Article in Journal of bacteriology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 60 citations in OpenAlex.
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- Fosfomycin Resistance: An Update on the Anthropogenic Impact Through Agriculture.Pathogens (Basel, Switzerland) · 2025Review
- Genomic and Functional Characterization of Multidrug-ResistantAntibiotics (Basel, Switzerland) · 2025Article
- Antechodynamics and Antechokinetics: Dynamics and Kinetics of Antibiotic Resistance Biomolecules.Biomolecules · 2025Review
- Antibiotic-induced stress responses in Gram-negative bacteria and their role in antibiotic resistance.The Journal of antimicrobial chemotherapy · 2025Review
- Aminoglycoside heteroresistance inmBio · 2024Article
- Breaking Barriers: Exploiting Envelope Biogenesis and Stress Responses to Develop Novel Antimicrobial Strategies in Gram-Negative Bacteria.Pathogens (Basel, Switzerland) · 2024Review
- Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Nutrient Limitation SensitizesACS infectious diseases · 2023Article
- Inactivation ofMicrobiology spectrum · 2023Article
- The Two-Component System CpxRA Represses Salmonella Pathogenicity Island 2 by Directly Acting on theMicrobiology spectrum · 2022Article
- Differences in Fosfomycin Resistance Mechanisms between Pseudomonas aeruginosa andAntimicrobial agents and chemotherapy · 2022Review
- Metabolic fitness landscapes predict the evolution of antibiotic resistance.Nature ecology & evolution · 2021Article
- Progress Overview of Bacterial Two-Component Regulatory Systems as Potential Targets for Antimicrobial Chemotherapy.Antibiotics (Basel, Switzerland) · 2020Review
- The Inactivation of Enzymes Belonging to the Central Carbon Metabolism Is a Novel Mechanism of Developing Antibiotic Resistance.mSystems · 2020Article
- Complex Response of the CpxAR Two-Component System to β-Lactams on Antibiotic Resistance and Envelope Homeostasis inAntimicrobial agents and chemotherapy · 2020Article
- In vitro activity of AST-120 that suppresses indole signaling in Escherichia coli, which attenuates drug tolerance and virulence.PloS one · 2020Article
- Whole-genome sequence analyses ofPeerJ · 2020Article
- CpxR-Dependent Thermoregulation of Serratia marcescens PrtA Metalloprotease Expression and Its Contribution to Bacterial Biofilm Formation.Journal of bacteriology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although fosfomycin is an old antibiotic, it has resurfaced with particular interest. The antibiotic is still effective against many pathogens that are resistant to other commonly used antibiotics. We have found that fosfomycin resistance of enterohemorrhagic Escherichia coli (EHEC) O157:H7 is controlled by the bacterial two-component signal transduction system CpxAR. A cpxA mutant lacking its phosphatase activity results in constitutive activation of its cognate response regulator, CpxR, and fosfomycin resistance. We have shown that fosfomycin resistance requires CpxR because deletion of the cpxR gene in the cpxA mutant restores fosfomycin sensitivity. We have also shown that CpxR directly represses the expression of two genes, glpT and uhpT, which encode transporters that cotransport fosfomycin with their native substrates glycerol-3-phosphate and glucose-6-phosphate, and repression of these genes leads to a decrease in fosfomycin transport into the cpxA mutant. However, the cpxA mutant had an impaired growth phenotype when cultured with glycerol-3-phosphate or glucose-6-phosphate as a sole carbon substrate and was outcompeted by the parent strain, even in nutrient-rich medium. This suggests a trade-off between fosfomycin resistance and the biological fitness associated with carbon substrate uptake. We propose a role for the CpxAR system in the reversible control of fosfomycin resistance. This may be a beneficial strategy for bacteria to relieve the fitness burden that results from fosfomycin resistance in the absence of fosfomycin.
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Registered trials
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