Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 56, Issue 8, Pages 4463-4465Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.06354-11
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LFF571 is a novel semisynthetic thiopeptide and potent inhibitor of Gram-positive bacteria. We report that the antibacterial activity of LFF571 against Clostridium difficile is due to inhibition of translation. Single-step mutants of C. difficile with reduced susceptibility to LFF571 were selected at frequencies of <4.5 x 10(-11) to 1.2 x 10(-9). Sequencing revealed a G260E substitution in the thiopeptide-binding pocket of elongation factor Tu. Importantly, this mutation did not confer cross-resistance to clinically used antimicrobials. These results support the development of LFF571 as a treatment for C. difficile infection.
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