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Background  Dissemination of antimicrobial resistance genes has become an important public health and biodefense threat. Plasmids are important contributors to the rapid acquisition of antibiotic resistance by pathogenic bacteria.    Principal Findings  The nucleotide sequence of the  Klebsiella pneumoniae  multiresistance plasmid pMET1 comprises 41,723 bp and includes Tn 1331.2 , a transposon that carries the  bla   TEM-1  gene and a perfect duplication of a 3-kbp region including the  aac(6′)-Ib ,  aadA1 , and  bla   OXA-9  genes. The replication region of pMET1 has been identified. Replication is independent of DNA polymerase I, and the replication region is highly related to that of the cryptic  Yersinia pestis  91001 plasmid pCRY. The potential partition region has the general organization known as the  parFG  locus. The self-transmissible pMET1 plasmid includes a type IV secretion system consisting of proteins that make up the mating pair formation complex (Mpf) and the DNA transfer (Dtr) system. The Mpf is highly related to those in the plasmid pCRY, the mobilizable high-pathogenicity island from  E. coli  ECOR31 (HPI ECOR31 ), which has been proposed to be an integrative conjugative element (ICE) progenitor of high-pathogenicity islands in other  Enterobacteriaceae  including  Yersinia  species, and ICE Kp1 , an ICE found in a  K. pneumoniae  strain causing primary liver abscess. The Dtr MobB and MobC proteins are highly related to those of pCRY, but the endonuclease is related to that of plasmid pK245 and has no significant homology with the protein of similar function in pCRY. The region upstream of  mobB  includes the putative  oriT  and shares 90% identity with the same region in the HPI ECOR31 .    Conclusions  The comparative analyses of pMET1 with pCRY, HPI ECOR31 , and ICE Kp1  show a very active rate of genetic exchanges between  Enterobacteriaceae  including  Yersinia  species, which represents a high public health and biodefense threat due to transfer of multiple resistance genes to pathogenic  Yersinia  strains.

Klebsiella pneumoniae Multiresistance Plasmid pMET1: Similarity with the Yersinia pestis Plasmid pCRY and Integrative Conjugative Elements