ArticleAntimicrobial agents and chemotherapy2014
Serratia marcescens arn, a PhoP-regulated locus necessary for polymyxin B resistance.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Pharmacokinetics of polymyxin B in different populations: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- Carbapenem-ResistantAntibiotics (Basel, Switzerland) · 2026Review
- Prevalence of mutations associated with tolerance to chlorhexidine and other cationic biocides amongMicrobiology (Reading, England) · 2025Article
- Mechanisms of Polymyxin Resistance in Acid-Adapted EnteroinvasiveMicroorganisms · 2024Article
- Identification and Functional Analysis of ncRNAs Regulating Intrinsic Polymyxin Resistance in FoodborneMicroorganisms · 2024Article
- Polymyxins: recent advances and challenges.Frontiers in pharmacology · 2024Review
- Characterization of the Arn lipopolysaccharide modification system essential for zeamine resistance unveils its new roles in Dickeya oryzae physiology and virulence.Molecular plant pathology · 2023Article
- The genomic characterization of carbapenem-resistantJAC-antimicrobial resistance · 2023Article
- Intrinsic Resistance to Colistin in the GenusJournal of clinical microbiology · 2023Article
- Translational protein RpsE as an alternative target for novel nucleoside analogues to treat MDR Enterobacter cloacae ATCC 13047: network analysis and molecular dynamics study.World journal of microbiology & biotechnology · 2023Article
- Review
- Occurrence ofAntibiotics (Basel, Switzerland) · 2022Article
- High-level carbapenem tolerance requires antibiotic-induced outer membrane modifications.PLoS pathogens · 2022Article
- Colistin Resistance Mechanisms in HumanAntibiotics (Basel, Switzerland) · 2022Article
- A cyclic adenosine monophosphate response element-binding protein inhibitor enhances the antibacterial activity of polymyxin B by inhibiting the ATP hydrolyzation activity of CrrB.Frontiers in pharmacology · 2022Article
- A Genome-Scale Antibiotic Screen in Serratia marcescens Identifies YdgH as a Conserved Modifier of Cephalosporin and Detergent Susceptibility.Antimicrobial agents and chemotherapy · 2021Article
- Antibiotics Used in Empiric Treatment of Ocular Infections Trigger the Bacterial Rcs Stress Response System Independent of Antibiotic Susceptibility.Antibiotics (Basel, Switzerland) · 2021Article
- Serratia marcescens RamA Expression Is under PhoP-Dependent Control and Modulates Lipid A-Related Gene Transcription and Antibiotic Resistance Phenotypes.Journal of bacteriology · 2021Article
- Rescuing the Last-Line Polymyxins: Achievements and Challenges.Pharmacological reviews · 2021Review
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polymyxins, which are increasingly being used to treat infections caused by multidrug-resistant bacteria, perform poorly against Serratia marcescens. To investigate the underlying mechanisms, Tn5 mutagenesis was performed and two mutants exhibiting increased polymyxin B (PB) susceptibility were isolated. The mutants were found to have Tn5 inserted into the arnB and arnC genes. In other bacteria, arnB and arnC belong to the seven-gene arn operon, which is involved in lipopolysaccharide (LPS) modification. LPSs of arn mutants had greater PB-binding abilities than that of wild-type LPS. Further, we identified PhoP, a bacterial two-component response regulator, as a regulator of PB susceptibility in S. marcescens. By the reporter assay, we found PB- and low-Mg2+-induced expression of phoP and arn in the wild-type strain but not in the phoP mutant. Complementation of the phoP mutant with the full-length phoP gene restored the PB MIC and induction by PB and low Mg2+ levels, as in the wild type. An electrophoretic mobility shift assay (EMSA) further demonstrated that PhoP bound directly to the arn promoter. The PB challenge test confirmed that pretreatment with PB and low Mg2+ levels protected S. marcescens from a PB challenge in the wild-type strain but not in the phoP mutant. Real-time reverse transcriptase-PCR also indicated that PB serves as a signal to regulate expression of ugd, a gene required for LPS modification, in S. marcescens through a PhoP-dependent pathway. Finally, we found that PB-resistant clinical isolates displayed greater expression of arnA upon exposure to PB than did susceptible isolates. This is the first report to describe the role of S. marcescens arn in PB resistance and its modulation by PB and Mg2+ through the PhoP protein.
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