Dissemination of bla _OXA-23 in Acinetobacter spp. in China: Main Roles of Conjugative Plasmid pAZJ221 and Transposon Tn 2009

Abstract

bProduction of the OXA-23 carbapenemase is the most common reason for the increasing carbapenem resistance in Acinetobacter spp. This study was conducted to reveal the genetic basis of bla OXA-23 dissemination in Acinetobacter spp. in China. A total of 63 carbapenem-resistant OXA-23-producing Acinetobacter sp. isolates, representing different backgrounds, were selected from 28 hospitals in 18 provinces for this study. Generally, two patterns of plasmids carrying bla OXA-23 were detected according to S1-nuclease pulsed-field gel electrophoresis and Southern blot hybridization. A ca. 78-kb plasmid, designated pAZJ221, was found in 23 Acinetobacter baumannii and three Acinetobacter nosocomialis isolates, while a novel ca. 50-kb plasmid was carried by only two other A. baumannii isolates. Three of these isolates had an additional copy of bla OXA-23 on the chromosome. Transformation of the two plasmids succeeded, but only pAZJ221 was conjugative. Plasmid pAZJ221 was sequenced completely and found to carry no previously known resistance genes except bla OXA-23 . The bla OXA-23 gene of the remaining 35 isolates was chromosome borne. The bla OXA-23 genetic environments were correlated with Tn2009 in 57 isolates, Tn2008 in 5 isolates, and Tn2006 in 1 isolate. The MIC values for the carbapenems with these isolates were not significantly associated with the genomic locations or the copy numbers of bla OXA-23 . Overall, these observations suggest that the plasmid pAZJ221 and Tn2009 have effectively contributed to the wide dissemination of bla OXA-23 in Acinetobacter spp. in China and that horizontal gene transfer may play an important role in dissemination of the bla OXA-23 gene.

Molecular epidemiology of bla OXA-23 -producing carbapenem-resistant Acinetobacter baumannii in a single institution over a 65-month period in north China

“…Chromosomal locations of bla oxa-23 make it less likely for A.baumannii to lose caarbapenem resistance. Investigation of OXA-23 producing A.baumannii isolates collected from 28 hospitals in 18 provinces of China showed that OXA-23 was mainly located on a ca.78-kb plasmid or on a chromosome [41]. …”

Evolution of AbGRI2-0, the Progenitor of the AbGRI2 Resistance Island in Global Clone 2 of Acinetobacter baumannii

“…Consequently the MAR, XAR, and panresistant GC2 isolates seen in many countries today are all derived from a single cell that had acquired both AbGRI1 and AbGRI2. Current XAR GC2 isolates have usually retained resistance to at least some of the older antibiotics but have gained resistance to newer antibiotics, either through mutations or by acquisition of new genes in transposons that are located in plasmids or inserted into the chromosome (e.g., oxa23 or aphA6) (13,24,25). The AbGRI3 island carrying armA is also a later addition found only in some GC2 isolates (13,14).…”

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.…”

“…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).…”