rplC T460C Identified as a Dominant Mutation in Linezolid-Resistant Mycobacterium tuberculosis Strains

Molecular Mycobacteriology, Research Center Borstel, Borstel, Germany.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 02/2012; 56(5):2743-5. DOI: 10.1128/AAC.06227-11
Source: PubMed

ABSTRACT The ribosomal L3 protein was identified as a novel target in linezolid (LZD)-resistant Mycobacterium tuberculosis strains. Next-generation sequencing confirmed rplC T460C as the sole mutation in an LZD-resistant M. tuberculosis H37Rv strain selected in vitro. Sequencing analysis revealed the rplC T460C mutation in eight further LZD-resistant isolates (three in vitro-selected mutants and five patient isolates, including isolates from three different patients that developed LZD resistance during treatment) but in none of the susceptible control strains (n = 84).

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Available from: Jörn Kalinowski, Sep 28, 2015
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    • "Consistent with previous reports [14] [30], mutation in the 23S rRNA gene may, alone or in combination with other mutations, cause high-level LNZ resistance (32 ␮g/mL). However, LNZ-resistant isolates carrying the T460C mutation in rplC (16 ␮g/mL) exhibited slightly higher resistance than that from the previous literature (range 4–16 ␮g/mL) [14]. In addition, we first identified the non-synonymous substitution His155Asp in the peptidyl transferase centre of rplC conferring low-level LNZ resistance (2 ␮g/mL). "
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