title: Synthetic interaction between the TipN polarity factor and an AcrAB-family efflux pump implicates cell polarity in bacterial drug resistance.
abstract: Quinolone antibiotics are clinically important drugs that target bacterial DNA replication and chromosome segregation. Although the AcrAB-family efflux pumps generally protect bacteria from such drugs, the physiological role of these efflux systems and their interplay with other cellular events are poorly explored. Here, we report an intricate relationship between antibiotic resistance and cell polarity in the model bacterium Caulobacter crescentus. We show that a polarity landmark protein, TipN, identified by virtue of its ability to direct flagellum placement to the new cell pole, protects cells from toxic misregulation of an AcrAB efflux pump through a cis-encoded nalidixic acid-responsive transcriptional repressor. Alongside the importance of polarity in promoting the inheritance and activity of virulence functions including motility, we can now ascribe to it an additional role in drug resistance that is distinct from classical efflux mechanisms.
authors.affiliation: Department of Microbiology & Molecular Medicine, Institute of Genetics & Genomics in Geneva (iGE3), Faculty of Medicine/CMU, University of Geneva, Rue Michel Servet 1, 1211 Genève 4, Switzerland.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Kirkpatrick
authors.affiliation: Department of Microbiology & Molecular Medicine, Institute of Genetics & Genomics in Geneva (iGE3), Faculty of Medicine/CMU, University of Geneva, Rue Michel Servet 1, 1211 Genève 4, Switzerland. Electronic address: patrick.viollier@unige.ch.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Viollier
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016935:Caulobacter crescentus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D016764:Cell Polarity / Q000187:drug effects*; D002939:Ciprofloxacin / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009268:Nalidixic Acid / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009268:Nalidixic Acid; D002939:Ciprofloxacin