Author:
Yeung Amy T. Y.,Janot Laure,Pena Olga M.,Neidig Anke,Kukavica-Ibrulj Irena,Hilchie Ashley,Levesque Roger C.,Overhage Joerg,Hancock Robert E. W.
Abstract
ABSTRACTPseudomonas aeruginosais an opportunistic pathogen that is a major cause of respiratory tract and other nosocomial infections. The sensor kinase CbrA is a central regulator of carbon and nitrogen metabolism andin vitroalso regulates virulence-related processes inP. aeruginosa. Here, we investigated the role of CbrA in two murine models of infection. In both peritoneal infections in leukopenic mice and lung infection models, thecbrAmutant was less virulent since substantially larger numbers ofcbrAmutant bacteria were required to cause the same level of infection as wild-type or complemented bacteria. In contrast, in the chronic rat lung model thecbrAmutant grew and persisted as well as the wild type, indicating that the decrease ofin vivovirulence of thecbrAmutant did not result from growth deficiencies on particular carbon substrates observedin vitro. In addition, a mutant in the cognate response regulator CbrB showed no defect in virulence in the peritoneal infection model, ruling out the involvement of certain alterations of virulence properties in thecbrAmutant including defective swarming motility, increased biofilm formation, and cytotoxicity, since these alterations are controlled through CbrB. Further investigations indicated that the mutant was more susceptible to uptake by phagocytesin vitro, resulting in greater overall bacterial killing. Consistent with the virulence defect, it took a smaller number ofDictyostelium discoideumamoebae to kill thecbrAmutant than to kill the wild type. Transcriptional analysis of thecbrAmutant duringD. discoideuminfection led to the conclusion that CbrA played an important role in the iron metabolism, protection ofP. aeruginosaagainst oxidative stress, and the regulation of certain virulence factors.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
23 articles.
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