Molecular mechanisms of β-lactam resistance in carbapenemase-producing Klebsiella pneumonia from Sri Lanka

Jarrad Hall, Enoka Corea, H.D. Anusha Sanjeewani, Tim Inglis

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    Carbapenemases are increasingly important antimicrobial resistance determinants. Little is known about the carbapenem resistance mechanisms in Sri Lanka. We examined 22 carbapenemresistant Klebsiella pneumoniae from Sri Lanka to determine their β-lactam resistance mechanisms. The predominant resistance mechanisms we detected in this study were OXA-181, NDM-1 carbapenemases and extended-spectrum β-lactamase CTX-M-15. All isolates were then genotyped by pulsed-field gel electrophoresis, variable-number tandem repeat sequence analysis and multilocus sequence typing, and seven distinct genotypes were observed. Five OXA-181- positive Klebsiella pneumoniae isolates were genotypically related to an isolate of Indian origin. Multilocus sequence typing found that these related isolates belong to ST-14, which has been associated with dissemination of OXA-181 from the Indian subcontinent. Other genotypes we discovered were ST-147 and ST-340, also associated with intercontinental spread of carbapenemases of suspected subcontinental origin. The major porin genes ompK35 and ompK36 from these isolates had insertions, deletions and substitutions. Some of these were exclusive to strains within single pulsotypes. We detected one ompK36 variant, ins AA134- 135GD, in six ST-14- and six ST-147, blaOXA-181-positive isolates. This porin mutation was an independent predictor of high-level meropenem resistance in our entire Sri Lankan isolate collection (P=0.0030). Analysis of the Sri Lankan ST-14 and ST-147 ins AA134-135GDpositive isolates found ST-14 was more resistant to meropenem than other isolates (mean MIC: 32±0 μg ml-1 and 20±9.47 μg ml-1, respectively, P=0.0277). The likely international transmission of these carbapenem resistance determinants highlights the need for regional collaboration and prospective surveillance of carbapenem-resistant Enterobacteriaceae. © 2014 The Authors.
    Original languageEnglish
    Pages (from-to)1087-1092
    JournalJournal of Medical Microbiology
    Volume63
    Issue numberPART 8
    DOIs
    Publication statusPublished - 2014

    Fingerprint

    meropenem
    Lactams
    Sri Lanka
    Carbapenems
    Klebsiella pneumoniae
    Multilocus Sequence Typing
    Porins
    Genotype
    Minisatellite Repeats
    Tandem Repeat Sequences
    Pulsed Field Gel Electrophoresis
    Enterobacteriaceae
    Sequence Analysis
    Mutation
    Genes
    Asp(5)-oxytocin
    carbapenemase

    Cite this

    Hall, Jarrad ; Corea, Enoka ; Anusha Sanjeewani, H.D. ; Inglis, Tim. / Molecular mechanisms of β-lactam resistance in carbapenemase-producing Klebsiella pneumonia from Sri Lanka. In: Journal of Medical Microbiology. 2014 ; Vol. 63, No. PART 8. pp. 1087-1092.
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    abstract = "Carbapenemases are increasingly important antimicrobial resistance determinants. Little is known about the carbapenem resistance mechanisms in Sri Lanka. We examined 22 carbapenemresistant Klebsiella pneumoniae from Sri Lanka to determine their β-lactam resistance mechanisms. The predominant resistance mechanisms we detected in this study were OXA-181, NDM-1 carbapenemases and extended-spectrum β-lactamase CTX-M-15. All isolates were then genotyped by pulsed-field gel electrophoresis, variable-number tandem repeat sequence analysis and multilocus sequence typing, and seven distinct genotypes were observed. Five OXA-181- positive Klebsiella pneumoniae isolates were genotypically related to an isolate of Indian origin. Multilocus sequence typing found that these related isolates belong to ST-14, which has been associated with dissemination of OXA-181 from the Indian subcontinent. Other genotypes we discovered were ST-147 and ST-340, also associated with intercontinental spread of carbapenemases of suspected subcontinental origin. The major porin genes ompK35 and ompK36 from these isolates had insertions, deletions and substitutions. Some of these were exclusive to strains within single pulsotypes. We detected one ompK36 variant, ins AA134- 135GD, in six ST-14- and six ST-147, blaOXA-181-positive isolates. This porin mutation was an independent predictor of high-level meropenem resistance in our entire Sri Lankan isolate collection (P=0.0030). Analysis of the Sri Lankan ST-14 and ST-147 ins AA134-135GDpositive isolates found ST-14 was more resistant to meropenem than other isolates (mean MIC: 32±0 μg ml-1 and 20±9.47 μg ml-1, respectively, P=0.0277). The likely international transmission of these carbapenem resistance determinants highlights the need for regional collaboration and prospective surveillance of carbapenem-resistant Enterobacteriaceae. {\circledC} 2014 The Authors.",
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    Molecular mechanisms of β-lactam resistance in carbapenemase-producing Klebsiella pneumonia from Sri Lanka. / Hall, Jarrad; Corea, Enoka; Anusha Sanjeewani, H.D.; Inglis, Tim.

    In: Journal of Medical Microbiology, Vol. 63, No. PART 8, 2014, p. 1087-1092.

    Research output: Contribution to journalArticle

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    AB - Carbapenemases are increasingly important antimicrobial resistance determinants. Little is known about the carbapenem resistance mechanisms in Sri Lanka. We examined 22 carbapenemresistant Klebsiella pneumoniae from Sri Lanka to determine their β-lactam resistance mechanisms. The predominant resistance mechanisms we detected in this study were OXA-181, NDM-1 carbapenemases and extended-spectrum β-lactamase CTX-M-15. All isolates were then genotyped by pulsed-field gel electrophoresis, variable-number tandem repeat sequence analysis and multilocus sequence typing, and seven distinct genotypes were observed. Five OXA-181- positive Klebsiella pneumoniae isolates were genotypically related to an isolate of Indian origin. Multilocus sequence typing found that these related isolates belong to ST-14, which has been associated with dissemination of OXA-181 from the Indian subcontinent. Other genotypes we discovered were ST-147 and ST-340, also associated with intercontinental spread of carbapenemases of suspected subcontinental origin. The major porin genes ompK35 and ompK36 from these isolates had insertions, deletions and substitutions. Some of these were exclusive to strains within single pulsotypes. We detected one ompK36 variant, ins AA134- 135GD, in six ST-14- and six ST-147, blaOXA-181-positive isolates. This porin mutation was an independent predictor of high-level meropenem resistance in our entire Sri Lankan isolate collection (P=0.0030). Analysis of the Sri Lankan ST-14 and ST-147 ins AA134-135GDpositive isolates found ST-14 was more resistant to meropenem than other isolates (mean MIC: 32±0 μg ml-1 and 20±9.47 μg ml-1, respectively, P=0.0277). The likely international transmission of these carbapenem resistance determinants highlights the need for regional collaboration and prospective surveillance of carbapenem-resistant Enterobacteriaceae. © 2014 The Authors.

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