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Small molecule suppression of carbapenem resistance in NDM-1 producing Klebsiella pneumoniae.

ABSTRACT: The already considerable global public health threat of multi-drug resistant Gram-negative bacteria has become even more of a concern following the emergence of New-Delhi metallo-β-lactamase (NDM-1) producing strains of Klebsiella pneumoniae and other Gram-negative bacteria. As an alternative approach to the traditional development of new bactericidal entities, we have identified a 2-aminoimidazole derived small molecule that acts as an antibiotic adjuvant and is able to suppress resistance of a NDM-1 producing strain of K. pneumoniae to imipenem and meropenem, in addition to suppressing resistance of other β-lactam non-susceptible K. pneumoniae strains. The small molecule is able to lower carbapenem minimum inhibitory concentrations by up to 16-fold while exhibiting little bactericidal activity itself.

SUBMITTER: Worthington RJ

PROVIDER: S-EPMC3405495 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Small molecule suppression of carbapenem resistance in NDM-1 producing Klebsiella pneumoniae.

Worthington Roberta J RJ Bunders Cynthia A CA Reed Catherine S CS Melander Christian C

ACS medicinal chemistry letters 20120204 5

The already considerable global public health threat of multi-drug resistant Gram-negative bacteria has become even more of a concern following the emergence of New-Delhi metallo-β-lactamase (NDM-1) producing strains of Klebsiella pneumoniae and other Gram-negative bacteria. As an alternative approach to the traditional development of new bactericidal entities, we have identified a 2-aminoimidazole derived small molecule that acts as an antibiotic adjuvant and is able to suppress resistance of a ...[more]

PMID: 22844552

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