Global Molecular Epidemiology of IMP-Producing Enterobacteriaceae

Abstract

International data on the molecular epidemiology of Enterobacteriaceae with IMP carbapenemases are lacking. We performed short-read (Illumina) whole-genome sequencing on a global collection of 38 IMP-producing clinical Enterobacteriaceae (2008 to 2014). IMP-producing Enterobacteriaceae (7 varieties within 11 class 1 integrons) were mainly present in the South Pacific and Asia. Specific bla_IMP-containing integrons (In809 with bla_IMP-4, In722 with bla_IMP-6, and In687 with bla_IMP-14) were circulating among different bacteria in countries such as Australia, Japan, and Thailand. In1312 with bla_IMP-1 was present in Klebsiella pneumoniae from Japan and Citrobacter freundii from Brazil. Klebsiella pneumoniae (n = 22) was the most common species; clonal complex 14 (CC14) from Philippines and Japan was the most common clone and contained In1310 with bla_IMP-26 and In1321 with bla_IMP-6 The Enterobacter cloacae complex (n = 9) consisted of Enterobacter hormaechei and E. cloacae cluster III. CC78 (from Taiwan) containing In73 with bla_IMP-8 was the most common clone among the E. cloacae complex. This study highlights the importance of surveillance programs using the latest molecular techniques for providing insight into the characteristics and global distribution of Enterobacteriaceae with bla_IMP genes.

Keywords: Enterobacteriaceae; IMP; metallo-β-lactamases; molecular epidemiology.

FIG 1

Global distribution of IMP-producing Enterobacteriaceae isolates in this study. Numbers beside circles indicate IMP subtypes.

FIG 2

Phylogenetic tree of IMP-producing K. pneumoniae. This maximum-likelihood phylogram is based on a 4,437,167-bp core genome and a total of 417,610 SNPs. The core genome was identified using K. pneumoniae subsp. pneumoniae ATCC BAA-2146 as a reference genome. The tree included 22 study isolates and 5 reference strains (marked with asterisks). The tree is rooted by using the outgroup of Klebsiella quasipneumoniae ATCC 700603, and asterisks indicate bootstrap support of >90% from 100 replicates. In the subspecies column, Klebsiella variicola and K. quasipneumoniae (marked with asterisks) are not subspecies of K. pneumoniae but distinct species. ST2286 and ST2289 were novel types found in this study. A CC marked with red distributed internationally. OmpK35 and OmpK36 columns indicate predicted mutation of porins: W, wild; D, deficient (due to a premature stop codon); V, variant associated with increased MIC of carbapenems; U, variant with unknown significance. Virulence genes of clbA-R (collibactin), iroBCDN (salmochelin), and rmpA and/or rmpA2 were sought but not found.

FIG 3

Phylogenetic tree of IMP-producing Enterobacter spp. This maximum-likelihood phylogram is based on a 1,803,217-bp core genome and a total of 478,902 SNPs. The core genome was identified using E. cloacae subsp. cloacae ATCC 13047 as a reference genome. The tree included 9 study isolates and 6 reference strains (marked with asterisks). The tree is rooted by using the outgroup of Enterobacter aerogenes KCTC 2190, and asterisks indicate bootstrap support of >90% from 100 replicates. ST512, ST514, and ST520 were novel types found in this study.

FIG 4

Phylogenetic tree of IMP-producing Citrobacter spp. This maximum-likelihood phylogram is based on a 2,410,533-bp core genome and a total of 609,249 SNPs. The core genome was identified using C. freundii CAV1321 as a reference genome. The tree included 4 study isolates and 8 reference strains (marked with asterisks). The tree is rooted by using the outgroup of Citrobacter koseri ATCC BAA-895, and asterisks indicate bootstrap support of >90% from 100 replicates. STs 97 to 100 were novel types found in this study.