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Title: Worldwide emergence of colistin resistance in Klebsiella pneumoniae from healthy humans and patients in Lao PDR, Thailand, Israel, Nigeria and France owing to inactivation of the PhoP/PhoQ regulator mgrB: An epidemiological and molecular study
Authors: Abiola Olumuyiwa Olaitan
Seydina M. Diene
Marie Kempf
Meryem Berrazeg
Sofiane Bakour
Sushim Kumar Gupta
Boupha Thongmalayvong
Kongsap Akkhavong
Silaphet Somphavong
Phimpha Paboriboune
Kittipong Chaisiri
Chalit Komalamisra
Olawale Olufemi Adelowo
Obasola Ezekiel Fagade
Omowunmi Abosede Banjo
Adeyeye James Oke
Amos Adler
Marc Victor Assous
Serge Morand
Didier Raoult
Jean Marc Rolain
Unite de Recherche sur les Maladies Infectieuses et Tropicales emergentes
CHU Angers
National Institutes of Health, Bethesda
Centre d'Infectiologie Christophe Mérieux du Laos
Mahidol University
University of Ibadan
Bowen University Teaching Hospital
Israel Ministry of Health
Shaare Zedek Medical Center
Institut des Sciences de l'Evolution UMR 5554
Keywords: Medicine
Issue Date: 1-Jan-2014
Citation: International Journal of Antimicrobial Agents. Vol.44, No.6 (2014), 500-507
Abstract: © 2014 Elsevier B.V. and the International Society of Chemotherapy. The emergence of colistin-resistant Klebsiella pneumoniae (CRKP) is a major public health concern worldwide. In this study, the prevalence and molecular basis of colistin resistance in CRKP isolated from healthy individuals and patients in Lao PDR, Thailand, Nigeria and France were investigated. Stool samples were screened by culture for the presence of colistin-resistant Klebsiella spp. Whole-genome sequence analysis was used to decipher the molecular mechanism of colistin resistance in a blaNDM-1-positive in vitro-selected CRKP mutant. PCR amplification and sequencing of the mgrB genetic environment was performed for all CRKP isolates as well as control colistin-susceptible K. pneumoniae (CSKP) isolates recovered from the same stools. A total of 869 stool samples were screened for colistin-resistant Klebsiella spp., yielding 32 CRKP and 2 colistin-resistant Klebsiella oxytoca. Comparative whole-genome sequence analysis revealed that an in vitro-selected CRKP mutant had an insertion sequence in its mgrB gene, as well as missense mutations in other selected clones. Of the 34 colistin-resistant Klebsiella spp. isolates, 14 (41.2%; 13 CRKP and 1 K. oxytoca) from the four countries also had various defects in their mgrB genes, but no such defects were found in the CSKP controls (P < 10-4). Few mutations were observed in pmrAB compared with 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 ≥40% of colistin resistance among the CRKP isolates observed in this study.
ISSN: 18727913
Appears in Collections:Scopus 2011-2015

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