PLoS pathogens, 2018-05, Vol.14 (5), p.e1007030
2018
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- A global regulatory system links virulence and antibiotic resistance to envelope homeostasis in Acinetobacter baumannii
- Ist Teil von
- PLoS pathogens, 2018-05, Vol.14 (5), p.e1007030
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The nosocomial pathogen Acinetobacter baumannii is a significant threat due to its ability to cause infections refractory to a broad range of antibiotic treatments. We show here that a highly conserved sensory-transduction system, BfmRS, mediates the coordinate development of both enhanced virulence and resistance in this microorganism. Hyperactive alleles of BfmRS conferred increased protection from serum complement killing and allowed lethal systemic disease in mice. BfmRS also augmented resistance and tolerance against an expansive set of antibiotics, including dramatic protection from β-lactam toxicity. Through transcriptome profiling, we showed that BfmRS governs these phenotypes through global transcriptional regulation of a post-exponential-phase-like program of gene expression, a key feature of which is modulation of envelope biogenesis and defense pathways. BfmRS activity defended against cell-wall lesions through both β-lactamase-dependent and -independent mechanisms, with the latter being connected to control of lytic transglycosylase production and proper coordination of morphogenesis and division. In addition, hypersensitivity of bfmRS knockouts could be suppressed by unlinked mutations restoring a short, rod cell morphology, indicating that regulation of drug resistance, pathogenicity, and envelope morphogenesis are intimately linked by this central regulatory system in A. baumannii. This work demonstrates that BfmRS controls a global regulatory network coupling cellular physiology to the ability to cause invasive, drug-resistant infections.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7374, 1553-7366eISSN: 1553-7374DOI: 10.1371/journal.ppat.1007030Titel-ID: cdi_plos_journals_2049929658
- Format
- –
- Schlagworte
- Acinetobacter, Acinetobacter baumannii, Acinetobacter baumannii - genetics, Acinetobacter baumannii - metabolism, Acinetobacter Infections - pathology, Alleles, Amides, Animals, Anti-Bacterial Agents - pharmacology, Antibiotic resistance, Antibiotics, Bacteria, Bacterial Proteins - metabolism, beta-Lactam Resistance - genetics, beta-Lactamases - metabolism, Biofilms - growth & development, Biology and Life Sciences, Cell division, Cell morphology, Cell walls, Cellular communication, Cytology, Disease, Drug resistance, Drug Resistance, Bacterial - genetics, Drug Resistance, Bacterial - immunology, Drug Resistance, Bacterial - physiology, Drug Resistance, Multiple, Bacterial - genetics, E coli, Escherichia coli, Evolution, Female, Gene expression, Gene Expression Regulation, Bacterial - genetics, Gene Expression Regulation, Bacterial - immunology, Gene regulation, Genetic aspects, Health aspects, Homeostasis, Homeostasis - drug effects, Hospitals, Hypersensitivity, Infections, Integrated software, Kinases, Lesions, Medicine, Medicine and Health Sciences, Mice, Mice, Inbred C57BL, Microbial drug resistance, Microbial Sensitivity Tests, Molecular biology, Morphogenesis, Morphology, Mutation, Nosocomial infection, Pathogenicity, Pathogens, Phenotypes, Physical Sciences, Physiology, Pneumonia, Signal transduction, Signal Transduction - drug effects, Stress response, Toxicity, Transcription, Transcription factors, Transcriptome - genetics, Transcriptome - immunology, Virulence, Virulence (Microbiology), Virulence - drug effects, Virulence - immunology