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    Thr202Ala in thyA Is a Marker for the Latin American Mediterranean Lineage of the Mycobacterium tuberculosis Complex Rather than Para-Aminosalicylic Acid Resistance

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    Antimicrob. Agents Chemother.-2010-Feuerriegel-4794-8.pdf
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    Type
    Article
    Authors
    Feuerriegel, S.
    Koser, C.
    Trube, L.
    Archer, John A.C. cc
    Rusch Gerdes, S.
    Richter, E.
    Niemann, S.
    KAUST Department
    Computational Bioscience Research Center (CBRC)
    Date
    2010-08-30
    Online Publication Date
    2010-08-30
    Print Publication Date
    2010-11-01
    Permanent link to this record
    http://hdl.handle.net/10754/554095
    
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    Abstract
    Single nucleotide polymorphisms (SNPs) involved in the development of resistance represent powerful markers for the rapid detection of first- and second-line resistance in clinical Mycobacterium tuberculosis complex (MTBC) isolates. However, the association between particular mutations and phenotypic resistance is not always clear-cut, and phylogenetic SNPs have been misclassified as resistance markers in the past. In the present study, we investigated the utility of a specific polymorphism in thyA (Thr202Ala) as a marker for resistance to para-aminosalicyclic acid (PAS). Sixty-three PAS-susceptible MTBC strains comprising all major phylogenetic lineages, reference strain H37Rv, and 135 multidrug-resistant (MDR) strains from Germany (comprising 8 PAS-resistant isolates) were investigated for the presence of Thr202Ala. In both strain collections, the Thr202Ala SNP was found exclusively in strains of the Latin American Mediterranean (LAM) lineage irrespective of PAS resistance. Furthermore, PAS MICs (0.5 mg/liter) for selected LAM strains (all containing the SNP) and non-LAM strains (not containing the SNP), as well as the results of growth curve analyses performed in liquid 7H9 medium in the presence of increasing PAS concentrations (0 to 2.0 mg/liter), were identical. In conclusion, our data demonstrate that the Thr202Ala polymorphism in thyA is not a valid marker for PAS resistance but, instead, represents a phylogenetic marker for the LAM lineage of the M. tuberculosis complex. These findings challenge some of the previous understanding of PAS resistance and, as a consequence, warrant further in-depth investigations of the genetic variation in PAS-resistant clinical isolates and spontaneous mutants.
    Citation
    Thr202Ala in thyA Is a Marker for the Latin American Mediterranean Lineage of the Mycobacterium tuberculosis Complex Rather than Para-Aminosalicylic Acid Resistance 2010, 54 (11):4794 Antimicrobial Agents and Chemotherapy
    Publisher
    American Society for Microbiology
    Journal
    Antimicrobial Agents and Chemotherapy
    DOI
    10.1128/AAC.00738-10
    PubMed ID
    20805400
    PubMed Central ID
    PMC2976163
    Additional Links
    http://aac.asm.org/cgi/doi/10.1128/AAC.00738-10
    ae974a485f413a2113503eed53cd6c53
    10.1128/AAC.00738-10
    Scopus Count
    Collections
    Articles; Computational Bioscience Research Center (CBRC); Computational Bioscience Research Center (CBRC)

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