Intraspecies Transfer of the Chromosomal Acinetobacter baumannii bla _NDM-1 Carbapenemase Gene

Abstract

The species Acinetobacter baumannii is one of the most important multidrug-resistant human pathogens. To determine its virulence and antibiotic resistance determinants, the genome of the nosocomial bla NDM-1 -positive A. baumannii strain R2090 originating from Egypt was completely sequenced. Genome analysis revealed that strain R2090 is highly related to the communityacquired Australian A. baumannii strain D1279779. The two strains belong to sequence type 267 (ST267). Isolate R2090 harbored the chromosomally integrated transposon Tn125 carrying the carbapenemase gene bla NDM-1 that is not present in the D1279779 genome. To test the transferability of the metallo-␤-lactamase (MBL) gene region, the clinical isolate R2090 was mated with the susceptible A. baumannii recipient CIP 70.10, and the carbapenem-resistant derivative R2091 was obtained. Genome sequencing of the R2091 derivative revealed that it had received an approximately 66-kb region comprising the transposon Tn125 embedding the bla NDM-1 gene. This region had integrated into the chromosome of the recipient strain CIP 70.10. From the four known mechanisms for horizontal gene transfer (conjugation, outer membrane vesicle-mediated transfer, transformation, and transduction), conjugation could be ruled out, since strain R2090 lacks any plasmid, and a type IV secretion system is not encoded in its chromosome. However, strain R2090 possesses three putative prophages, two of which were predicted to be complete and therefore functional. Accordingly, it was supposed that the transfer of the resistance gene region from the clinical isolate R2090 to the recipient occurred by general transduction facilitated by one of the prophages present in the R2090 genome. Hence, phage-mediated transduction has to be taken into account for the dissemination of antibiotic resistance genes within the species A. baumannii.

Genomic analysis reveals the presence of a class D beta-lactamase with broad substrate specificity in animal bite associated Capnocytophaga species

“…In line with this analogy, it is possible that blaOXA347 could be transmitted via transposons to the more virulent and invasive C. canimorsus , although no such multidrug resistant C. canimorsus have been described. Notably, this mechanism of transmission was recently shown for the chromosomally encoded blaNDM-1 carbapenemase gene in Acinetobacter baumanii [14] and OXA48 carbapenemase in highly virulent E. coli [2]. …”

NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings

“…In addition to conjugation, which is the major mode of horizontal transfer of bla NDM in the Enterobacteriaceae, it has been found that OMVs of A. baumannii are able to mediate the intra-and interspecies transfer of bla NDM plasmids at high transformation frequencies (10 Ϫ5 to 10 Ϫ6 transformants in the total cell count [CFU per milliliter]) (23,60). General transduction facilitated by prophages present in the chromosome can also mediate the horizontal transfer of bla NDM between A. baumannii strains (61). More studies are required on this remarkable diversity of Acinetobacter strains carrying bla NDM and its relevance to the successful emergence of NDM across Gram-negative bacteria.…”

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

“…In Acinetobacter, the bla NDM -type genes are found to be located on either the plasmid or chromosome. Among NDM-producing A. baumannii, the bla NDM gene is usually reported to be found between two copies of the ISAba125 element, forming a composite transposon named Tn125 (158)(159)(160). Identification of a truncated form of this composite transposon in Enterobacteriaceae, while reported in its entire form in A. baumannii, strongly suggests that Acinetobacter spp.…”

“…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).…”