OXA-235, a Novel Class D β-Lactamase Involved in Resistance to Carbapenems in Acinetobacter baumannii

<jats:title>ABSTRACT</jats:title> <jats:p> We investigated the mechanism of carbapenem resistance in 10 <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Acinetobacter baumannii</jats:named-content> strains isolated from the United States and Mexico between 2005 and 2009. The detection of known metallo-β-lactamase or carbapenem-hydrolyzing oxacillinase (OXA) genes by PCR was negative. The presence of plasmid-encoded carbapenem resistance genes was investigated by transformation of <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">A. baumannii</jats:named-content> ATCC 17978. Shotgun cloning experiments and sequencing were performed, followed by the expression of a novel β-lactamase in <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">A. baumannii</jats:named-content> . 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) in 1 isolate each. The deduced amino acid sequences shared 85% identity with OXA-134, 54% to 57% identities 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. The expression of OXA-235 in <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">A. baumannii</jats:named-content> led to reduced carbapenem susceptibility, while cephalosporin MICs were unaffected. Genetic analysis revealed that <jats:italic>bla</jats:italic> <jats:sub>OXA-235</jats:sub> , <jats:italic>bla</jats:italic> <jats:sub>OXA-236</jats:sub> , and <jats:italic>bla</jats:italic> <jats:sub>OXA-237</jats:sub> were bracketed between two IS <jats:italic>Aba1</jats:italic> insertion sequences. In addition, the presence of these acquired β-lactamase genes might result from a transposition-mediated mechanism. This highlights the propensity of <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">A. baumannii</jats:named-content> to acquire multiple carbapenem resistance determinants. </jats:p>