Physiological role of BlaB and GOB metallo-beta-lactamases in Elizabethkingia meningoseptica

GONZÁLEZ LJ; LIMANSKY AS; VILA AJ

San Miguel de Tucumán

Congreso; XLV Reunión Anual. Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Elizabethkingia meningoseptica is an opportunistic pathogen associated with meningitis. This organism is resistant to all beta-lactams antibiotics, apparently because of three cromosomically encoded beta-lactamases: a serine-beta-lactamase CME, and two distantly related metallo-beta-lactamases (mbls), BlaB and GOB. All mbl-producing bacteria so far investigated produce a single mbl accompanying a serine-beta-lactamase. Given that the substrate profile exhibited by BlaB and GOB is similar, we decided to investigate the involvement of each of these mbls in carbapenem resistance in E. meningoseptica.Phenotypic assays suggested that resistance to carbapenems is exclusively associated with mbl production. RNA expression levels of blaCME, blaBlaB and blaGOB genes were similar, as assayed by qRT-PCR. Immunoprecipitation of GOB from an E. meningoseptica crude extract showed no diminution in imipenemase activity, indicating that resistance to imipenem depends primarily on BlaB. Expression analysis revealed an increase in levels of BlaB RNA as E. meningoseptica enters stationary phase. Intact cells activity against imipenem, however, showed a marked diminution in that stage.These results suggest that E. meningoseptica’s resistance to carbapenemes is due only to BlaB, being its beta-lactamase activity a secondary effect of some other cellular process. BlaB would be implicated in stationary phase metabolism.