Mutations in two component system (PhoPQ and PmrAB) in colistin resistant Klebsiella pneumoniae from North Indian tertiary care hospital
Colistin resistance in Gram negative bacteria is mainly attributed to chromosomal mutations in Two Component Systems(TCS) PhoPQ and PmrAB and plasmid-borne genes( mcr and its variants). The aim of this study was to understand the molecular basis of colistin resistance in Klebsiella pneumoniae and de...
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| Published in: | Journal of antibiotics Vol. 74; no. 7; pp. 450 - 457 |
|---|---|
| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
London
Nature Publishing Group UK
01-07-2021
Nature Publishing Group |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Colistin resistance in Gram negative bacteria is mainly attributed to chromosomal mutations in Two Component Systems(TCS) PhoPQ and PmrAB and plasmid-borne genes(
mcr
and its variants). The aim of this study was to understand the molecular basis of colistin resistance in
Klebsiella pneumoniae
and determine clonal transmission, in a North Indian tertiary care hospital over a 2.5 year period. Antimicrobial susceptibility was determined by Vitek and colistin resistance was confirmed by broth microdilution. Carbapenemases(
bla
KPC
, bla
VIM
, bla
IMP
, bla
NDM
, bla
OXA-48
) and
mcr
-1 screening was done by PCR. Mutations in chromosomal genes
mgrB, phoP, phoQ, pmrA, pmrB
were analysed. Sequence typing was performed by Multilocus sequence typing(MLST). OXA-48 was detected in thirteen isolates while three isolates co-expressed OXA-48 and NDM. The
mcr
-1 gene was absent in all 16 isolates. Deleterious mutations in
mgrB
included insertion sequences IS903 and ISkpn26 and a premature stop codon. A total of 18 point mutations were identified in PhoPQ and PmrAB TCS; of which, novel mutations were reported in
phoQ
(K46E, L322V, D152N, F373L, R249G),
pmrB
(P159R) and
pmrA
(D149L). Six different sequence types ST231, ST147, ST395, ST42, ST14 and ST101 were identified. Phylogenetic analysis showed that sequence types ST14, ST395 and ST147 are closely related to ST101 and all identified sequence types had a common ancestor ST231. Colistin resistance in
K. pneumoniae
was attributed to mutations in PhoPQ and PmrAB TCS, while location specific distribution of strains indicates clonal transmission. The results of this study will help in formulation of effective infection prevention and antimicrobial development strategies. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0021-8820 1881-1469 |
| DOI: | 10.1038/s41429-021-00417-2 |