title: Carbapenem resistance in Elizabethkingia meningoseptica is mediated by metallo-β-lactamase BlaB.
abstract: Elizabethkingia meningoseptica, a Gram-negative rod widely distributed in the environment, is resistant to most β-lactam antibiotics. Three bla genes have been identified in E. meningoseptica, coding for the extended-spectrum serine-β-lactamase CME (class D) and two unrelated wide-spectrum metallo-β-lactamases, BlaB (subclass B1) and GOB (subclass B3). E. meningoseptica is singular in being the only reported microorganism possessing two chromosomally encoded MBL genes. Real-time PCR and biochemical analysis demonstrate that the three bla genes are actively expressed in vivo as functional β-lactamases. However, while CME elicits cephalosporin resistance, BlaB is the only β-lactamase responsible for E. meningoseptica resistance to imipenem, as GOB activity is masked by higher cellular levels of BlaB. On the other hand, we demonstrate that bla(BlaB) expression is higher in the stationary phase or under conditions that mimic the nutrient-limiting cerebrospinal fluid colonized by E. meningoseptica in human meningitis.
authors.affiliation: Instituto de Biologia Molecular y Celular de Rosario, CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Lisandro J
authors.initials: LJ
authors.lastname: González
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Vila
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D015780:Carbapenems / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology; D045247:Chryseobacterium / Q000187:drug effects* / Q000235:genetics*; D017931:DNA Primers; D004274:DNA, Recombinant / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D047468:Immunoprecipitation; D012329:RNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D001618:beta-Lactamases / Q000235:genetics*; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D002511:Cephalosporins; D017931:DNA Primers; D004274:DNA, Recombinant; D012329:RNA, Bacterial; D047090:beta-Lactams; C410343:BLAB3 protein, Flavobacterium meningosepticum; D001618:beta-Lactamases; C558534:beta-lactamase GOB-1, Elizabethkingia meningoseptica