GES-11, a Novel Integron-Associated GES Variant in Acinetobacter baumannii

Abstract

New extended-spectrum ␤-lactamase GES-11 was detected in Acinetobacter baumannii BM4674. The enzyme conferred resistance to ␤-lactams, including aztreonam, and reduced susceptibility to carbapenems. The structural gene was part of a class 1 integron borne by self-transferable plasmid pIP847. GES-type ␤-lactamases have not been reported previously in A. baumannii.Acinetobacter baumannii is a predominant species associated with outbreaks of nosocomial infections, such as pneumonia, urinary tract infections, septicemia, and meningitis. Its clinical significance is due to its ability either to upregulate indigenous efflux pumps (5) or to acquire numerous resistance mechanisms (7) that lead to therapeutic failure. A rapid, global emergence of A. baumannii strains resistant to all ␤-lactams, including carbapenems, aminoglycosides, quinolones, tetracyclines-glycylcyclines, polymyxins, and trimethoprim-sulfamethoxazole, has been observed (1). A. baumannii clinical specimens resistant to all known antibiotics, including polymyxins, have been reported, illustrating the genetic flexibility of this pathogen (13).Resistance to ␤-lactams in A. baumannii is due mainly to the production of ␤-lactamases but can also result from several other mechanisms, including changes in outer membrane proteins, overexpression of multidrug efflux pumps, and alterations in the affinity or production of penicillin-binding proteins (9). ␤-Lactamases with carbapenemase activity, i.e., class D carbapenem-hydrolyzing oxacillinases or, less frequently, class B metallo-␤-lactamases, represent the major clinical concern. To the best of our knowledge, Ambler class A carbapenemases KPC, GES, SME, NMC, and IMI have not yet been reported in A. baumannii (18).A. baumannii BM4674 was isolated from the tibia fracture of a patient hospitalized at the Centre Hospitalier Universitaire in Nancy, France, in September 2008. MICs of antimicrobial agents for this strain were determined by Etest (AB Biodisk, Combourg, France) on Mueller-Hinton agar (bioMerieux, Marcy l'Etoile, France), and the breakpoints delivered by the Comité de l'Antibiogramme de la Société Française de Microbiologie were used for interpretations of results (3). A. baumannii BM4674 was resistant to all ␤-lactams, with decreased susceptibility to carbapenems (MIC imipenem ϭ 4 g/ ml; MIC meropenem ϭ 8 g/ml). It was also resistant to aminoglycosides, co-trimoxazole, quinolones, and chloramphenicol but remained susceptible to tetracyclines-glycylcyclines, colistin, and rifampin (rifampicin).The transfer of ␤-lactam resistance from A. baumannii BM4674 to A. baumannii BM4652 was performed by conjugation on solid medium, as described previously (11). Transconjugants selected on agar containing apramycin (80 g/ml) and ceftazidime (16 g/ml) were obtained at a high frequency of ca. 1 ϫ 10 Ϫ3 per recipient cell. They exhibited a broad spectrum of resistance to ␤-lactams, including aztreonam, diminished susceptibility to imipenem (MIC ϭ 0.75 g/ml) and meropenem (MIC ϭ 1.5 g/ml) compared to that of the recipi...

Multidrug-resistant Acinetobacter baumannii strains carrying the blaOxA-23 and the blaGES-11 genes in a neonatology center in Tunisia

“…OXA-type carbapenemases have predominated in A. baumannii, especially worldwide outbreaks of OXA-23 [1]. Recently the GES-1-like carbapenemases have also been reported for A. baumannii [9,14,23,24,25].…”

“…Since then, several GES-1 mutants have been detected in A. baumannii, such as GES-12, GES-14, and GES-22 [9,14,22,23,24]. a CLA, Clavulanic acid (4 mg/ml); TZB, Tazobactam (4 mg/ml).…”

“…GES-11 b-lactamase possesses increased activity against aztreonam [14,23]. However the bla GES-11 -carrying transconjugant showed reduced susceptibilities to carbapenems, suggesting the presence of weak hydrolysis of carbapenems by this enzyme potentiated by the efflux overproduction in A. baumannii BM4547 [14,23].So, GES-11 may contribute to play a synergistic role toward resistance to carbapenems in A. baumannii, together with OXA-23 [14].Several studies reported the association between the bla GES and bla OxA-like gene, especially bla GES-11 and bla OxA-23 genes [14,23,24]. To our knowledge, however, carbapenem resistant A. baumannii isolate producing the carbapenem-hydrolyzing oxacillinase OXA-23 in association with the GES-11 class A b-lactamase in Tunisia have not been reported previously.…”

Role of ISAba1 and ISAba125 in governing the expression of bla ADC in clinically relevant Acinetobacter baumannii strains resistant to cephalosporins

“…The cephalosporin and co-amoxiclav synergy test was negative for all the strains. They were also negative for the presence of bla PER , bla VEB and bla GES genes (Moubareck et al, 2009).…”

“…The cephalosporins used for this assay were ceftazidime, cefotaxime, cefpodoxime and cefepime. A PCR was also performed for the detection of bla PER , bla VEB and bla GES (Moubareck et al, 2009). …”