Loss of the 29-Kilodalton Outer Membrane Protein in the Presence of OXA-51–Like Enzymes inAcinetobacter baumanniiIs Associated with Decreased Imipenem Susceptibility

Abstract

Carbapenem resistance in Acinetobacter baumannii is increasing these days. We investigated the roles of outer membrane proteins and efflux pumps in carbapenem resistance of A. baumannii which showed no carbapenemase activity in modified Hodge test. Among 58 carbapenem-resistant isolates collected from the Korea University Medical Center between January 2002 and March 2006, 17 isolates showed negative results in modified Hodge test. In outer membrane protein analysis, loss of the 29-kDa protein band was related with higher imipenem minimum inhibitory concentrations especially in the presence of OXA-51-like enzymes. Efflux pump-mediated carbapenem resistance was found in one out of the 17 isolates (5.9%). All of the 58 carbapenem-resistant strains and 5 of the 10 carbapenem-susceptible strains had OXA-51-like carbapenemase genes, suggesting that OXA-51-like enzymes may be naturally existing in A. baumannii and have very weak carbapenem hydrolyzing activity.

High prevalence of OXA-143 and alteration of outer membrane proteins in carbapenem-resistant Acinetobacter spp. isolates in Brazil

“…Oxacillinases have a lower carbapenem hydrolysing activity compared with MBLs, but they are still the most frequent carbapenemases described in this genus of bacteria. Even with a low carbapenem hydrolysing activity compared with MBLs, the oxacillinases have been identified as enzymes that most frequently confer imipenem resistance in Acinetobacter [10,23].…”

“…Different mechanisms of resistance to carbapenems have been reported, including degradation of the drug by ␤-lactamases, diminished permeability of the outer membrane and, to a lesser extent, overexpression of efflux pumps and changes in the target site owing to modification of penicillin-binding proteins [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Usually, when the minimum inhibitory concentration (MIC) of Table 1 Specific primers used in the study.…”

Horizontal Gene Transfer and Assortative Recombination within the Acinetobacter baumannii Clinical Population Provide Genetic Diversity at the Single carO Gene, Encoding a Major Outer Membrane Protein Channel

“…Still, A. baumannii clinical strains bearing IS-mediated carO interruptions have so far been detected only among carbapenem-resistant isolates (21,26,29). Thus, the IS-mediated inactivation of carO, or the HGT-mediated exchange of particular carO variants, by reducing carbapenem influx through the OM may act synergistically with other mechanisms present in some genetic backgrounds (1,12,13,18,20,21,34,35,38,39,47,49,51), therefore resulting in an increased fitness phenotype under carbapenem pressure. The possible selected combinations are currently under study in our laboratory.…”

“…However, the relatively low increases in imipenem sensitivity resulting from the expression of even the most efficient carO variants, in addition to the intrinsically high imipenem sensitivity of ATCC 17978 ⌬carO cells bearing only the plasmid vector (see MIC above), strongly indicate that an OM channel(s) other than CarO, allowing the efficient permeation of carbapenems, is also present in this multidrug-sensitive strain. In this context, other authors have associated the loss of different OM proteins to carbapenem resistance in different A. baumannii clinical isolates (13,20,25,35,38,51). The possible roles and contributions of these OM proteins to the acquisition of carbapenem resistance phenotypes in A. baumannii await further clarification.…”

Efflux-Mediated Antibiotic Resistance in Acinetobacter spp

“…The role of AdeABC in carbapenem resistance is controversial. Susceptibility testing with and without efflux pump inhibitors (EPI), such as carbonyl cyanide m-chlorophenylhydrazone (CCCP), reserpine, 1-(1-naphthylmethyl)-piperazine (NMP), and phenyl-arginine-␤-naphthylamide (PA␤N), showed no differences in carbapenem activity (6,53,54), whereas a 2-to 8-fold reduction in resistance was found in other work when an EPI was added, suggesting involvement of efflux (27,33,34,48). Overexpression of AdeABC con- (23).…”