RT Journal Article
SR Electronic
T1 Emergence of carbapenem, beta-lactamase inhibitor and cefoxitin resistant lineages from a background of ESBL-producing Klebsiella pneumoniae and K. quasipneumoniae highlights different evolutionary mechanisms
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 283291
DO 10.1101/283291
A1 Heinz, Eva
A1 Ejaz, Hasan
A1 Scott, Josefin Bartholdson
A1 Wang, Nancy
A1 Guanjaran, Shruti
A1 Pickard, Derek
A1 Wilksch, Jonathan
A1 Cao, Hanwei
A1 ul-Haq, Ikram
A1 Dougan, Gordon
A1 Strugnell, Richard A
YR 2018
UL http://biorxiv.org/content/early/2018/03/15/283291.abstract
AB Klebsiella pneumoniae is recognised as a major threat to public health, with increasing emergence of multidrug-resistant lineages including strains resistant to all available antibiotics. We present an in-depth analysis of 178 extended-spectrum beta-lactamase (ESBL)-producing Klebsiella strains, with a high background diversity and two dominant lineages, as well as several equally resistant lineages with less prevalence. Neither the overall resistance profile nor the virulence factors explain the prevalence of some lineages; we observe several putative hypervirulence factors across the population, including a reduced virulence plasmid, but this does not correlate with expansion of one or few highly virulent and resistant lineages. Phenotypic analysis of the profiles of resistance traits shows that the vast majority of the phenotypic resistance profiles can be explained by detailed genetic analyses. The main discrepancies are observed for beta-lactams combined with beta-lactamase inhibitors, where most, but not all, resistant strains carry a carbapenemase or ampC. Complete genomes for six selected strains, including three of the 21 carbapenem-resistant ones, are reported, which give detailed insights into the early evolution of the bla-NDM-1 enzyme, a carbapenemase that was first reported in 2009 and is now globally distributed. Whole-genome based high-resolution analyses of the dominant lineages suggests a very dynamic picture of gene transfer and selection, with phenotypic changes due to plasmid acquisition and chromosomal changes, and emphasize the need to monitor the bacteria at high resolution to understand the rise of high-risk clones, which cannot be explained by obvious differences in resistance profiles or virulence factors.Importance Carbapenem-resistant and extended-spectrum beta-lactamase (ESBL) carrying Enterobacteriaceae were recently highlighted as critical priority fo the development of new treatments by the WHO. Klebsiella pneumoniae is a member of the Enterobacteriaceae and has seen a dramatic rise in clinical relevance due to its uncanny ability to accumulate multidrug-resistance plasmids. We present a detailed analysis of a set of ESBL-resistant K. pneumoniae clinical isolates, and our high-resolution whole-genome sequence analyses highlight that acquisition of drug resistances is not a one-way street in K. pneumoniae, but a highly dynamic process of gain and loss, and that the most successful lineages in the clinic are not necessarily the most resistant or most virulent ones. Analysis of the virulence potential also shows that these strains harbour some, but not all, hallmarks of hypervirulent strains, emphasizing that it is not a clear distinction between hypervirulent and other strains, but equally in flux.