title: Complete sequencing of pNDM-HK encoding NDM-1 carbapenemase from a multidrug-resistant Escherichia coli strain isolated in Hong Kong.
abstract: BACKGROUND
  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 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.
  
  
  METHODS
  We characterized the first NDM-1 producing E. coli isolate recovered in Hong Kong. The plasmid encoding the metallo-β-lactamase gene was sequenced.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  The 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.
authors: Department of Microbiology, The University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China. plho@hkucc.hku.hk
authors: Pak Leung
authors: PL
authors: Ho
authors: Wai U
authors: WU
authors: Lo
authors: Man Kiu
authors: MK
authors: Yeung
authors: Chi Ho
authors: CH
authors: Lin
authors: Kin Hung
authors: KH
authors: Chow
authors: Irene
authors: I
authors: Ang
authors: Amy Hin Yan
authors: AH
authors: Tong
authors: Jessie Yun-Juan
authors: JY
authors: Bao
authors: Si
authors: S
authors: Lok
authors: Janice Yee Chi
authors: JY
authors: Lo
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D004926:Escherichia coli / Q000201:enzymology*; D006723:Hong Kong; D008969:Molecular Sequence Data; D010957:Plasmids; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase