Author(s): Rémy A Bonnin 1 , Laurent Poirel 1 2 , Patrice Nordmann [*] 3
[beta]-lactamase; antibiotic resistance; carbapenemase; Gram-negative rods
Members of the genus Acinetobacter seem to have the ability to quite rapidly acquire resistance to new antibiotics  . The rise of resistance to broad-spectrum antibiotics such as aminoglycosides, expanded-spectrum cephalosporins, carbapenems and tigecycline in Acinetobacter baumannii has left few therapeutic options  . The main problem corresponds to the rise of carbapenem resistance in A. baumannii , which is almost always identified in multidrug-resistant clinical isolates  . Until now, A. baumannii has been considered a final reservoir of antibiotic resistance genes by acquisition of foreign DNA from different sources, particularly from other Gram-negative species. Many resistance genes have been identified in A. baumannii including those encoding extended-spectrum [beta]-lactamases (PER-, Guiana extended-spectrum [beta]-lactamase [GES] and VEB type) and aminoglycoside resistance genes [1,4] . The acquisition of those genes is often related to an integration of foreign DNA originating from other clinical species (Enterobacteriaceae and Pseudomonas aeruginosa ) [1,2,4-7] .
Carbapenem resistance in A. baumannii
Genes encoding metallo-[beta]-lactamases of verona metallo-[beta]-lactamase- and imipenemase types, as well as those encoding class A carbapenemases ( Klebsiella pneumonia carbapenemase or GES), are other examples of acquisition of foreign resistance genes as a source of carbapenem resistance in A. baumannii  . Analysis of the genetic structures surrounding those carbapenemase genes reveals that they are not specific to Acinetobacter . The identified genetic structures argue for a transfer from Enterobacteriaceae and P. aeruginosa to A. baumannii .
The most important source of carbapenem resistance in A. baumannii is the production of carbapenem-hydrolyzing Ambler class D [beta]-lactamases (CHDL)  . Five different subgroups of acquired CHDLs have been identified, namely oxacillinase, class D [beta]-lactamase (OXA)-23, -40, -58, -143 and -235 [2,7,8] . These five CHDL groups are specific to the Acinetobacter species and are not usually identified in other clinically relevant species, such as in Enterobacteriaceae and in P. aeruginosa [2,7] . In contrast to what is observed for other types of carbapenemase genes (those encoding the carbapenemases K. pneumonia carbapenemase, GES, verona metallo-[beta]-lactamase and imipenemase), CHDL-encoding genes are associated with insertion sequences (IS) identified in Acinetobacter species (e.g., ISAba1 ). The natural progenitor of one of these carbapenemase subgroups (OXA-23) has been identified as being Acinetobacter radioresistens  . To date, this corresponds to one of the few examples of a resistance gene originating from an Acinetobacter species and targeting another Acinetobacter species.
The case of the bla NDM genes
The bla NDM-1 gene is one of the latest carbapenemase genes to have been reported. They have now been extensively reported in Enterobacteriaceae ( Escherichia coli and K. pneumoniae ), first from India, Pakistan and Bangladesh, and then from the rest of the world [10-12] . The occurrence of the bla NDM-1 gene in the environment has also been evidenced in India, particularly among environmental Gram-negative species  . Sequencing of a bla NDM-1 -bearing plasmid, as part of the analysis of the resistosome of a multidrug-resistant E. coli , led to the identification of a remnant of ISAba125 , located...