Thr202Ala in thyA Is a Marker for the Latin American Mediterranean Lineage of the Mycobacterium tuberculosis Complex Rather than Para-Aminosalicylic Acid Resistance
KAUST DepartmentComputational Bioscience Research Center (CBRC)
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AbstractSingle 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.
CitationThr202Ala 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
PublisherAmerican Society for Microbiology
PubMed Central IDPMC2976163
- [Mutations in the thymidylate synthase gene is a major mechanism in the para-aminosalicylic acid resistance of M. tuberculosis].
- Authors: Zhang ZD, Zhao YL, Li ZH, Jia HY, Liu YH, Chen X, Liu ZQ, Du BP, Xing AY, Ma Y
- Issue date: 2007 Sep
- The folate pathway is a target for resistance to the drug para-aminosalicylic acid (PAS) in mycobacteria.
- Authors: Rengarajan J, Sassetti CM, Naroditskaya V, Sloutsky A, Bloom BR, Rubin EJ
- Issue date: 2004 Jul
- Molecular genetics of para-aminosalicylic acid resistance in clinical isolates and spontaneous mutants of Mycobacterium tuberculosis.
- Authors: Mathys V, Wintjens R, Lefevre P, Bertout J, Singhal A, Kiass M, Kurepina N, Wang XM, Mathema B, Baulard A, Kreiswirth BN, Bifani P
- Issue date: 2009 May
- [Frontier of mycobacterium research--host vs. mycobacterium].
- Authors: Okada M, Shirakawa T
- Issue date: 2005 Sep
- A Pyrosequencing assay for rapid recognition of SNPs in Mycobacterium tuberculosis embB306 region.
- Authors: Isola D, Pardini M, Varaine F, Niemann S, Rüsch-Gerdes S, Fattorini L, Orefici G, Meacci F, Trappetti C, Rinaldo Oggioni M, Orrù G, LONG-DRUG study group.
- Issue date: 2005 Jul