Antimicrob Agents Chemother. 2013 Jan;57(1):633-6.

Characterization of OXA-204, a carbapenem-hydrolyzing class D β-lactamase from Klebsiella pneumoniae.

Potron A, Nordmann P, Poirel L.

Service de Bactériologie-Virologie, INSERM U914 Emerging Resistance to Antibiotics, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine et Université Paris-Sud, K. Bicêtre, France.

Abstract

A Klebsiella pneumoniae clinical isolate recovered in Tunisia showed resistance to all b-lactams and decreased susceptibility to carbapenems. K. pneumoniae 204 expressed the carbapenem-hydrolyzing b-lactamase OXA-204, differing from OXA-48 by two amino acid substitutions (Gln98His and Thr99Arg, class D b-lactamase (DBL) numbering). OXA-48 and OXA-204 shared similar resistance profiles, hydrolyzing carbapenems but sparing broad-spectrum cephalosporins. The blaOXA-204 gene was located onto a ca. 150-kb IncA/C-type plasmid, which also carried the blaCMY-4 gene. The blaOXA-204 gene was associated with an ISEcp1 element, whereas the blaOXA-48 genes are usually associated with IS1999.

PMID: 23114766

Supplement

Carbapenems are often the last therapeutic option for treating infections due to multidrug resistant Gram-negatives rods. Enterobacteriaceae which are the main source of bacterial infection in humans may be resistant to carbapenems thanks to production of carbapenem-hydrolyzing enzymes (carbapenemases). The main types of enterobacterial carbapenemases are KPC- NDM/IMP/VIM and  OXA-48-type carbapenemases (1). The carbapenemase OXA-48 producers are spreading in Europe since 2010, mostly originated from countries surrounding the Mediterranean area such as Turkey,  Libya Tunisia, Morocco, and Algeria (3). Until now, it was believed that OXA-48 producers from those countries express an unique type of carbapenemase, OXA-48, which gene was located on a single ca. 62-kb plasmid (3). We characterize here a novel OXA-48-type carbapenemase (OXA-204), recovered from clinical isolate from Tunisia. OXA-204 possesses an hydrolysis spectrum similar to that of OXA-48 that includes penicillins and carbapenems (Figure 1). The blaOXA-204 gene was associated to the insertion sequence ISEcp1. Analysis of the DNA sequence located upstream of the blaOXA-204 gene indicated that they were different from those located upstream of the blaOXA-48 gene. Although OXA-204 differs from OXA-48 by a very few amino-acids, the origin of the blaOXA-204 gene and the blaOXA-48 gene differs, being the chromosome of Shewanella xiamenensis and Shewanella oneidensis (2), respectively (both being water-borne Gram-negative bacterial species. Therefore, this study shows the diversity of the reservoir of the  blaOXA-48 like genes. In addition, it shows that epidemic of OXA-48-like carbapenemases in North Africa is not limited to that of OXA-48.

Patrice Nordmann-1

Figure 1. Disk diffusion susceptibility testing of an Escherichia coli strain producing carbapenemase OXA-204. AMX : amoxicillin, AMC : amoxicillin + clavulanic acid, ATM : aztreonam, CAZ : ceftazidime, CTX : cefotaxime, FEP : cefepime, FOX : cefoxitine, ETP : ertapenem, IMP : imipenem, K: kanamycin, MEM : meropenem, MOX : moxalactam, PIP : piperacillin, TEM : temocillin, TIC : ticarcillin, TCC : ticarcillin + clavulanic acid, TZP : piperacillin + tazobactam. Of note, a full susceptibility to extended-spectrum cephalosporins , a decreased susceptibility to carbapenems and resistance to amoxillin/clavulanic acid which is  a susceptibility pattern suggestive of OXA-48 like producers.

References

1      Nordmann P, Dortet L, Poirel L. Carbapenem resistance in Enterobacteriaceae; here is the storm! Trends Mol Med. 2012 May18(5):263-72.

2      Poirel L, Héritier C, Nordmann P. Chromosome-encoded Ambler class D ß-lactamase of Shewanella oneidensis as progenitor of carbapenem-hydrolyzing oxacillinase. Antimicrob Agents Chemother. 2004 Jan;48(1):348-5.

3      Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: the phantom menace. J Antimicrob Chemother. 2012 Jul;67(7):1597-606.

 

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