Worldwide emergence of colistin resistance in Klebsiella pneumoniae from healthy humans and patients in Lao PDR, Thailand, Israel, Nigeria, and France due to inactivation of the PhoP/PhoQ mgrB regulator: an epidemiological and molecular study. Klebsiella pneumoniae KPM_nasey

The emergence of colistin-resistant Klebsiella pneumoniae (CRKP) is a major public-health concern worldwide. We investigated the prevalence and molecular basis of colistin resistance in CRKP isolated from healthy individuals and patients in Lao PDR, Thailand, Nigeria, and France. Stool samples were screened by culture for the presence of CRKP. Whole-genome sequence analysis was used to decipher the molecular mechanism of colistin resistance in blaNDM-1 positive in vitro-selected CRKP mutant. PCR amplification and sequencing of the mgrB gene environment was performed for all CRKP isolates and control colistin-susceptible K. pneumoniae isolates recovered from the same stools. A total of 869 stool samples were screened for CRKP, yielding 32 CRKP and two colistin-resistant K. oxytoca. Comparative whole-genome sequence analysis revealed that the in vitro-selected CRKP mutant had an insertion sequence in its mgrB gene, as well as missense mutations in other selected clones. Fourteen (13 CRKP and one K. oxytoca) out of 34 (41.2%) isolates from the four countries also had various defects in their mgrB genes, but no such defects were found in the susceptible controls (p <10-4). Few mutations were observed in pmrAB compared to mgrB among the CRKP isolates. The worldwide emergence of CRKP is a major public-health concern; detection and surveillance of such strains are warranted to prevent an uncontrollable pandemic. Inactivation of the PhoP/PhoQ regulator gene (mgrB) is associated with at least 40% of colistin resistance among the CRKP isolates observed in this study.