ArticleNature2015
HipBA-promoter structures reveal the basis of heritable multidrug tolerance.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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Who cites it
133 citing papers in PubMed.
- Bacterial strategies for surviving antibiotics during urinary tract infection: could uropathogenic Escherichia coli be persisters?Nature reviews. Urology · 2026Review
- Article
- Association ofPathogens (Basel, Switzerland) · 2026Article
- Mechanism of persister formation in response to nitrogen starvation.Nature communications · 2026Article
- Heterogeneity in microbial antibiotic responses: genetic basis and within-host evolution.Trends in genetics : TIG · 2026Review
- Article
- Single-cell analysis reveals critical toxin/antitoxin ratio triggering persister resuscitation.Molecular systems biology · 2026Article
- A rational approach to discovering new persister control agents.Antimicrobial agents and chemotherapy · 2025Article
- Antibiotic tolerance and persistence in clinical isolates ofMicrobiology spectrum · 2025Article
- Article
- Recent advances in the understanding, detection and therapeutic targeting of bacterial recalcitrance.BMC microbiology · 2025Review
- Sonoporation-enhanced the antibacterial efficacy of aminoglycosides against Gram-negative persisters.World journal of microbiology & biotechnology · 2025Article
- Dogs fed raw meat-based diets are vectors of drug-resistant Salmonella infection in humans.Communications medicine · 2025Article
- Surviving Colonies ofAntibiotics (Basel, Switzerland) · 2025Article
- NrdR in Streptococcus and Listeria spp.: DNA Helix Phase Dependence of the Bacterial Ribonucleotide Reductase Repressor.Molecular microbiology · 2025Article
- Evidence for a Functional HipBA Toxin-Antitoxin System inInternational journal of molecular sciences · 2025Article
- A link between aging and persistence.Antimicrobial agents and chemotherapy · 2025Article
- Priestia megaterium cells are primed for surviving lethal doses of antibiotics and chemical stress.Communications biology · 2025Article
- Persistence phenotype of adherent-invasiveMicrobial cell (Graz, Austria) · 2025Article
- Recent Advances in Antimicrobial Resistance: Insights fromMicroorganisms · 2024Review
73 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
Abstract
Multidrug tolerance is largely responsible for chronic infections and caused by a small population of dormant cells called persisters. Selection for survival in the presence of antibiotics produced the first genetic link to multidrug tolerance: a mutant in the Escherichia coli hipA locus. HipA encodes a serine-protein kinase, the multidrug tolerance activity of which is neutralized by binding to the transcriptional regulator HipB and hipBA promoter. The physiological role of HipA in multidrug tolerance, however, has been unclear. Here we show that wild-type HipA contributes to persister formation and that high-persister hipA mutants cause multidrug tolerance in urinary tract infections. Perplexingly, high-persister mutations map to the N-subdomain-1 of HipA far from its active site. Structures of higher-order HipA-HipB-promoter complexes reveal HipA forms dimers in these assemblies via N-subdomain-1 interactions that occlude their active sites. High-persistence mutations, therefore, diminish HipA-HipA dimerization, thereby unleashing HipA to effect multidrug tolerance. Thus, our studies reveal the mechanistic basis of heritable, clinically relevant antibiotic tolerance.
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