title: The global regulator Crc modulates metabolism, susceptibility to antibiotics and virulence in Pseudomonas aeruginosa.
abstract: The capacity of a bacterial pathogen to produce a disease in a treated host depends on the former's virulence and resistance to antibiotics. Several scattered pieces of evidence suggest that these two characteristics can be influenced by bacterial metabolism. This potential relationship is particularly important upon infection of a host, a situation that demands bacteria adapt their physiology to their new environment, making use of newly available nutrients. To explore the potential cross-talk between bacterial metabolism, antibiotic resistance and virulence, a Pseudomonas aeruginosa model was used. This species is an important opportunistic pathogen intrinsically resistant to many antibiotics. The role of Crc, a global regulator that controls the metabolism of carbon sources and catabolite repression in Pseudomonas, was analysed to determine its contribution to the intrinsic antibiotic resistance and virulence of P. aeruginosa. Using proteomic analyses, high-throughput metabolic tests and functional assays, the present work shows the virulence and antibiotic resistance of this pathogen to be linked to its physiology, and to be under the control (directly or indirectly) of Crc. A P. aeruginosa strain lacking the Crc regulator showed defects in type III secretion, motility, expression of quorum sensing-regulated virulence factors, and was less virulent in a Dictyostelium discoideum model. In addition, this mutant strain was more susceptible to beta-lactams, aminoglycosides, fosfomycin and rifampin. Crc might therefore be a good target in the search for new antibiotics.
authors.affiliation: Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Linares
authors.forename: Renata
authors.initials: R
authors.lastname: Moreno
authors.forename: Alicia
authors.initials: A
authors.lastname: Fajardo
authors.forename: Laura
authors.initials: L
authors.lastname: Martínez-Solano
authors.forename: Ricardo
authors.initials: R
authors.lastname: Escalante
authors.forename: Fernando
authors.initials: F
authors.lastname: Rojo
authors.forename: José L
authors.initials: JL
authors.lastname: Martínez
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D057465:Catabolite Repression; D004023:Dictyostelium / Q000382:microbiology; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial; D005809:Genes, Regulator; D020543:Proteome; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D053038:Quorum Sensing; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D020543:Proteome; D012097:Repressor Proteins; D037521:Virulence Factors; C101896:crc protein, Pseudomonas