Carbapenem Resistance in Elizabethkingia meningoseptica Is Mediated by Metallo-β-Lactamase BlaB

Abstract

ABSTRACTElizabethkingia meningoseptica, a Gram-negative rod widely distributed in the environment, is resistant to most β-lactam antibiotics. Threeblagenes have been identified inE. 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. meningosepticais singular in being the only reported microorganism possessing two chromosomally encoded MBL genes. Real-time PCR and biochemical analysis demonstrate that the threeblagenes are actively expressedin vivoas functional β-lactamases. However, while CME elicits cephalosporin resistance, BlaB is the only β-lactamase responsible forE. meningosepticaresistance to imipenem, as GOB activity is masked by higher cellular levels of BlaB. On the other hand, we demonstrate thatblaBlaBexpression is higher in the stationary phase or under conditions that mimic the nutrient-limiting cerebrospinal fluid colonized byE. meningosepticain human meningitis.