Τίτλος:
Multifaceted mechanisms of colistin resistance revealed by genomic analysis of multidrug-resistant Klebsiella pneumoniae isolates from individual patients before and after colistin treatment
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objectives: Polymyxins (i.e., polymyxin B and colistin) are used as a last-line therapy to combat multidrug-resistant (MDR) Klebsiella pneumoniae. Worryingly, polymyxin resistance in K. pneumoniae is increasingly reported worldwide. This study identified the genetic variations responsible for high-level colistin resistance in MDR K. pneumoniae clinical isolates. Methods: Sixteen MDR K. pneumoniae isolates were obtained from stool samples of 8 patients before and after colistin treatment. Their genomes were sequenced on Illumina MiSeq to determine genetic variations. Results: Fifteen of 16 isolates harboured ISKpn26-like element insertion at nucleotide position 75 of mgrB, abolishing its negative regulation on phoPQ; while colistin-susceptible ATH7 contained intact mgrB and phoQ. Interestingly, each of the 7 mgrB-disrupted, colistin-susceptible isolates contained a nonsynonymous substitution in PhoQ (G39S, L239P, N253T or V446G), potentially impairing its function and intergenically suppressing the effect caused by mgrB inactivation. Additionally, three of the 7 corresponding mgrB-disrupted, colistin-resistant isolates harboured a secondary nonsynonymous substitution in PhoQ (N253P, D438H or T439P). Conclusions: This is the first report of phoQ mutations in mgrB-disrupted, colistin-susceptible K. pneumoniae clinical isolates. We also discovered multiple phoQ mutations in mgrB-disrupted, colistin-resistant strains. Our findings highlight the multifaceted molecular mechanisms of colistin resistance in K. pneumoniae. © 2019 The British Infection Association
Συγγραφείς:
Zhu, Y.
Galani, I.
Karaiskos, I.
Lu, J.
Aye, S.M.
Huang, J.
Yu, H.H.
Velkov, T.
Giamarellou, H.
Li, J.
Περιοδικό:
Journal of Infection
Εκδότης:
W.B. Saunders Ltd
Λέξεις-κλειδιά:
colistin; antiinfective agent; bacterial protein; colistin; membrane protein; PhoQ protein, Bacteria, amino acid substitution; antibiotic sensitivity; antibiotic therapy; Article; bacterial gene; bacterial genome; bacterium isolate; clinical article; colistin resistance; feces analysis; gene insertion sequence; gene mutation; genetic variability; genome analysis; genomics; human; mgrB gene; multidrug resistance; multidrug resistant Klebsiella pneumoniae; nonhuman; phoPQ gene; sequence analysis; drug effect; genetics; isolation and purification; Klebsiella infection; Klebsiella pneumoniae; microbial sensitivity test; multidrug resistance; transposon, Anti-Bacterial Agents; Bacterial Proteins; Colistin; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Membrane Proteins; Microbial Sensitivity Tests
DOI:
10.1016/j.jinf.2019.07.009
