Structure and context ofAcinetobactertransposons carrying theoxa23carbapenemase gene

Abstract

Theoxa23gene encoding the OXA-23 carbapenemase (and several minor variants of it) is widespread inAcinetobacter baumanniiclinical isolates and compromises treatment with carbapenem antibiotics. The gene is derived from the chromosome ofAcinetobacter radioresistenswhere it is an intrinsic gene, here designatedoxaAr InA. baumanniiand otherAcinetobacterspecies,oxa23is usually preceded by an IS, ISAba1, which supplies the strong promoter required for the gene to confer clinically relevant levels of resistance. TheoxaArgene appears to have been mobilized twice creating Tn2008and Tn2008B, both of which consist of a single ISAba1 and anA. radioresistens-derived fragment. Tn2006and Tn2009are clearly derived from Tn2008Band are each made up of Tn2008Bwith an additional segment of unknown origin and an additional ISAba1, creating a compound transposon. Tn2006, Tn2008and possibly Tn2008Bare globally disseminated, while Tn2009has as yet only been found in China. Of the four ISAba1-associated transposons, Tn2006has been most frequently observed worldwide and Tn2006in Tn6022, known as AbaR4, appears to contribute significantly to the dissemination ofoxa23 Moreover, AbaR4, Tn2006, Tn2008and Tn2009have each been found in conjugative plasmids, further facilitating their spread.

Occurrence of Diverse AbGRI1-Type Genomic Islands in Acinetobacter baumannii Global Clone 2 Isolates from South Korea

“…Various subtypes of AbGRI1-type GIs in GC2 are also clearly associated with multiple recombination events. bla OXA-23 coupled with ISAba1, which might have been introduced into the A. baumannii genome by recombination (3,8), was found only in isolates harboring AbGRI1-type GIs. Carbapenem resistance due to bla OXA-23 may confer a selective advantage.…”

“…28 isolates, respectively; denoted by Tn6022 ϩ T2006 or Tn6022 ϩ Tn2008B in Table 2), which are generally believed to reside in other chromosomal sites or plasmids (8). We extracted plasmids from the isolates and tested for the presence of bla in the plasmids by PCR.…”

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

“…Acinetobacter isolates have shown a complex interaction of multiple mechanisms of resistance to carbapenems, with the production of naturally occurring oxacillinases (OXA) and the absence of PBP2 being most commonly observed; for some isolates, an additional downregulation of porin expression and subsequent reduction in carbapenem entry has been observed (138). The predominant oxacillinases (OXA-23, OXA-24 or -40, OXA-51, OXA-58, and OXA-143) are responsible for the majority of phenotypic resistance to carbapenems detected in the United States, Latin America, Europe, Asia, and in many parts of the world (31,(139)(140)(141)(142)(143)(144)(145)(146)(147)(148)(149)(150). OXA-23 is a plasmid-or transposonencoded ␤-lactamase, while OXA-51 is a chromosome-based enzyme and is intrinsic to Acinetobacter.…”

“…OXA-24/40 can be chromosomal or plasmid based, and OXA-58 is plasmid encoded. These class D ␤-lactamases are not very robust carbapenemases, but the presence of an insertion sequence (IS) element, such as ISAbaI and ISAba9, increases expression of the carbapenemase significantly, resulting in clinical carbapenem resistance (140,148,(151)(152)(153)(154)(155).…”

“…Transposon-mediated passage of resistance mechanisms are well described, including those for AmpC cephalosporinases, OXA carbapenemases, KPC serine carbapenemases, and NDM or VIM metallo-carbapenemases, and aminoglycosides (101,135,136,147,148,150,155,158,159,(172)(173)(174)(175)(176)(177)(178). Indeed, transposon-mediated resistance to classically described antibiotic classes, including ␤-lactams, tetracyclines, aminoglycosides, and sulfonamides, had occurred in a global lineage of A. baumannii by the late 1970s; new resistance was subsequently acquired in transposon lineages in the 1980s as new antibiotics became available (136).…”