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Antimicrob Agents Chemother. OXA-235, a novel Class D Beta-Lactamase Involved in Resistance to Carbapenems in Acinetobacter baumannii
[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
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OXA-235, a novel Class D Beta-Lactamase Involved in Resistance to Carbapenems in Acinetobacter baumannii [PublishAheadOfPrint]
Higgins, P. G., Perez-Llarena, F. J., Zander, E., Fernandez, A., Bou, G., Seifert, H.
We investigated the mechanism of carbapenem resistance in 10 Acinetobacter baumannii strains isolated from the United States and Mexico between 2005 and 2009. Detection of known metallo-beta-lactamase or carbapenem-hydrolyzing oxacillinase (OXA) genes by PCR was negative. Presence of plasmid encoded carbapenem-resistance genes was investigated by transformation of A. baumannii ATCC 17978. Shotgun cloning experiments and sequencing were performed followed by expression of novel beta-lactamase in A. baumannii. Three novel OXA enzymes were identified; OXA-235 in 8 isolates and the amino acid variants OXA-236 (Glu173-Val) and OXA-237 (Asp208-Gly) were found in 1 isolate each. The deduced amino acid sequence shared 85% identity with OXA-134, 54%-57% identity with the acquired OXA-23, OXA-24, OXA-58, and OXA-143, and 56% identity with the intrinsic OXA-51, and thus represent a novel subclass of OXA. Expression of OXA-235 in A. baumannii led to reduced carbapenem susceptibility while cephalosporin MICs were unaffected. Genetic analysis revealed that bla<SUB>OXA-235</SUB>, bla<SUB>OXA-236</SUB> and bla<SUB>OXA-237</SUB> were bracketed between two ISAba1 insertion sequences. In addition, presence of these acquired beta-lactamase genes might result from a transposition-mediated mechanism. This highlights the propensity of A. baumannii to acquire multiple carbapenem-resistance determinants.
-Higgins, P. G., Perez-Llarena, F. J., Zander, E., Fernandez, A., Bou, G., Seifert, H.
We investigated the mechanism of carbapenem resistance in 10 Acinetobacter baumannii strains isolated from the United States and Mexico between 2005 and 2009. Detection of known metallo-beta-lactamase or carbapenem-hydrolyzing oxacillinase (OXA) genes by PCR was negative. Presence of plasmid encoded carbapenem-resistance genes was investigated by transformation of A. baumannii ATCC 17978. Shotgun cloning experiments and sequencing were performed followed by expression of novel beta-lactamase in A. baumannii. Three novel OXA enzymes were identified; OXA-235 in 8 isolates and the amino acid variants OXA-236 (Glu173-Val) and OXA-237 (Asp208-Gly) were found in 1 isolate each. The deduced amino acid sequence shared 85% identity with OXA-134, 54%-57% identity with the acquired OXA-23, OXA-24, OXA-58, and OXA-143, and 56% identity with the intrinsic OXA-51, and thus represent a novel subclass of OXA. Expression of OXA-235 in A. baumannii led to reduced carbapenem susceptibility while cephalosporin MICs were unaffected. Genetic analysis revealed that bla<SUB>OXA-235</SUB>, bla<SUB>OXA-236</SUB> and bla<SUB>OXA-237</SUB> were bracketed between two ISAba1 insertion sequences. In addition, presence of these acquired beta-lactamase genes might result from a transposition-mediated mechanism. This highlights the propensity of A. baumannii to acquire multiple carbapenem-resistance determinants.
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