Abstract
BackgroundThe emergence of plasmid-mediated carbapenemases, such as NDM-1 in Enterobacteriaceae is a major public health issue. Since they mediate resistance to virtually all β-lactam antibiotics and there is often co-resistance to other antibiotic classes, the therapeutic options for infections caused by these organisms are very limited.MethodologyWe characterized the first NDM-1 producing E. coli isolate recovered in Hong Kong. The plasmid encoding the metallo-β-lactamase gene was sequenced.Principal FindingsThe plasmid, pNDM-HK readily transferred to E. coli J53 at high frequencies. It belongs to the broad host range IncL/M incompatibility group and is 88803 bp in size. Sequence alignment showed that pNDM-HK has a 55 kb backbone which shared 97% homology with pEL60 originating from the plant pathogen, Erwina amylovora in Lebanon and a 28.9 kb variable region. The plasmid backbone includes the mucAB genes mediating ultraviolet light resistance. The 28.9 kb region has a composite transposon-like structure which includes intact or truncated genes associated with resistance to β-lactams (bla TEM-1, bla NDM-1, Δbla DHA-1), aminoglycosides (aacC2, armA), sulphonamides (sul1) and macrolides (mel, mph2). It also harbors the following mobile elements: IS26, ISCR1, tnpU, tnpAcp2, tnpD, ΔtnpATn1 and insL. Certain blocks within the 28.9 kb variable region had homology with the corresponding sequences in the widely disseminated plasmids, pCTX-M3, pMUR050 and pKP048 originating from bacteria in Poland in 1996, in Spain in 2002 and in China in 2006, respectively.SignificanceThe genetic support of NDM-1 gene suggests that it has evolved through complex pathways. The association with broad host range plasmid and multiple mobile genetic elements explain its observed horizontal mobility in multiple bacterial taxa.
Highlights
The development of carbapenem resistance among Enterobacteriaceae is a major public health threat because carbapenems are currently the cornerstone therapy for patients with serious and lifethreatening infections caused by strains producing extendedspectrum b-lactamases (ESBLs)
The NDM-1 gene was carried on a broad host range IncL/M plasmid
The plasmid might spread among members of the Enterobacteriaceae and Gram negative non-fermenters. This could partly explained its detection in many members of the Enterobacteriaceae family (E. coli, K. pneumoniae, E, aerogenes, E. cloacae, C. freundii, Morganella morganii and Providencia spp.) and A. baumannii [6,16,17]
Summary
The development of carbapenem resistance among Enterobacteriaceae is a major public health threat because carbapenems are currently the cornerstone therapy for patients with serious and lifethreatening infections caused by strains producing extendedspectrum b-lactamases (ESBLs). Many public health authorities have expressed serious concerns when an international group of researchers reported the findings for patients with infections by carbapenem-resistant Enterobacteriaceae (CRE) carrying the novel resistant gene, NDM-1 (for New Delhi metallo-b-lactamase) with a putative link to the Indian subcontinent, where the burden of CTX-M producing bacteria is substantial [6]. The emergence of plasmid-mediated carbapenemases, such as NDM-1 in Enterobacteriaceae is a major public health issue. Since they mediate resistance to virtually all b-lactam antibiotics and there is often co-resistance to other antibiotic classes, the therapeutic options for infections caused by these organisms are very limited
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