Elizabethkingia meningoseptica's resistance to carbapenemes, a case of redundancy?

GONZÁLEZ LJ; LIMANSKY AS; VILA AJ

Rosario, Santa Fe, Argentina

Congreso; V Congreso Argentino de Microbiología General. SAMIGE; 2008

Sociedad Argentina de Microbiología General

Elizabethkingia meningoseptica is a gram-negative rod widely distributed in nature. It is known to cause meningitis in premature and newborn infants. In adults, cases of pneumonia, endocarditis, postoperative bacteremia, and meningitis have been reported, usually associated with a severe underlying illness. The organism is usually multiresistant to antibiotics typically prescribed for treating gram-negative bacterial infections, including extended-spectrum beta-lactam agents and aminoglycosides, and thus constitutes a clinical concern.E. meningoseptica is resistant to all beta-lactams antibiotics, apparently as a consequence of the expression of three cromosomically encoded beta-lactamases: a class D serine-beta-lactamase CME, and two metallo-beta-lactamases (mbls), BlaB of subclass B1 and GOB of subclass B3. 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, CME being responsible for the hydrolysis of penicillins and cephalosporins. RNA expression of blaCME, blaBlaB and blaGOB genes was tested by qRT-PCR, revealing similar levels of transcripts for the three genes. Exposure of E. meningoseptica to imipenem and cefotaxime resulted in no induction of any of the bla genes. In stationary phase, the levels of BlaB RNA manifested an abrupt increase with respect to CME and GOB. Quantitative immunoprecipitation of GOB from an E. meningoseptica crude extract showed no diminution in imipenemase activity. These results suggest that GOB is not implicated in in vivo resistance to imipenem. Therefore, BlaB would be the mbl responsible of clinical resistance to carbapenems, probably implicated in a stationary-phase defense mechanism.  As for other subclass B3 enzymes, the role of GOB in the cell remains to be elucidated.