Intestinal bile acids induce a morphotype switch in vancomycin-resistant enterococcus that facilitates intestinal colonization
Autor: | Peter T. McKenney, Eric G. Pamer, Jinyuan Yan, Julien Vaubourgeix, Joao B. Xavier, Daniel Dannaoui, Simone Becattini, Peter J. Larson, Andrew Motzer, Sho Fujisawa, Nina Lampen |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
SIGMA-FACTOR
HOST VRE Enterococcus faecium medicine.disease_cause faecium Mice chemistry.chemical_compound Cecum 0302 clinical medicine 1108 Medical Microbiology SALTS STRESS-RESPONSE morphotype Diplococcus 0303 health sciences Virulence Bile acid SYSTEM WALKR faecalis medicine.anatomical_structure Carrier State Life Sciences & Biomedicine 0605 Microbiology Lithocholic acid Colon medicine.drug_class Immunology bile Colonisation resistance Biology Microbiology DAPTOMYCIN RESISTANCE Article Vancomycin-Resistant Enterococci Bile Acids and Salts 03 medical and health sciences Virology colonization resistance medicine microbiota Animals Vancomycin-resistant Enterococcus CHAIN-LENGTH CELL-SIZE Gram-Positive Bacterial Infections 030304 developmental biology Science & Technology BIOFILM FORMATION Biofilm biochemical phenomena metabolism and nutrition biology.organism_classification bacterial infections and mycoses chemistry Enterococcus Parasitology 030217 neurology & neurosurgery |
Zdroj: | 705.e5 Cell Host Microbe |
Popis: | Summary Vancomycin-resistant Enterococcus (VRE) are highly antibiotic-resistant and readily transmissible pathogens that cause severe infections in hospitalized patients. We discovered that lithocholic acid (LCA), a secondary bile acid prevalent in the cecum and colon of mice and humans, impairs separation of growing VRE diplococci, causing the formation of long chains and increased biofilm formation. Divalent cations reversed this LCA-induced switch to chaining and biofilm formation. Experimental evolution in the presence of LCA yielded mutations in the essential two-component kinase yycG/walK and three-component response regulator liaR that locked VRE in diplococcal mode, impaired biofilm formation, and increased susceptibility to the antibiotic daptomycin. These mutant VRE strains were deficient in host colonization because of their inability to compete with intestinal microbiota. This morphotype switch presents a potential non-bactericidal therapeutic target that may help clear VRE from the intestines of dominated patients, as occurs frequently during hematopoietic stem cell transplantation. |
Databáze: | OpenAIRE |
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