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

Handle URI:
http://hdl.handle.net/10754/554095
Title:
Thr202Ala in thyA Is a Marker for the Latin American Mediterranean Lineage of the Mycobacterium tuberculosis Complex Rather than Para-Aminosalicylic Acid Resistance
Authors:
Feuerriegel, S.; Koser, C.; Trube, L.; Archer, John A.C. ( 0000-0002-3302-3933 ) ; Rusch Gerdes, S.; Richter, E.; Niemann, S.
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.
KAUST Department:
Computational Bioscience Research Center (CBRC)
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
Issue Date:
30-Aug-2010
DOI:
10.1128/AAC.00738-10
PubMed ID:
20805400
PubMed Central ID:
PMC2976163
Type:
Article
ISSN:
0066-4804; 1098-6596
Additional Links:
http://aac.asm.org/cgi/doi/10.1128/AAC.00738-10
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorFeuerriegel, S.en
dc.contributor.authorKoser, C.en
dc.contributor.authorTrube, L.en
dc.contributor.authorArcher, John A.C.en
dc.contributor.authorRusch Gerdes, S.en
dc.contributor.authorRichter, E.en
dc.contributor.authorNiemann, S.en
dc.date.accessioned2015-05-18T21:24:14Zen
dc.date.available2015-05-18T21:24:14Zen
dc.date.issued2010-08-30en
dc.identifier.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 Chemotherapyen
dc.identifier.issn0066-4804en
dc.identifier.issn1098-6596en
dc.identifier.pmid20805400en
dc.identifier.doi10.1128/AAC.00738-10en
dc.identifier.urihttp://hdl.handle.net/10754/554095en
dc.description.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.en
dc.publisherAmerican Society for Microbiologyen
dc.relation.urlhttp://aac.asm.org/cgi/doi/10.1128/AAC.00738-10en
dc.rightsArchived with thanks to Antimicrobial Agents and Chemotherapyen
dc.titleThr202Ala in thyA Is a Marker for the Latin American Mediterranean Lineage of the Mycobacterium tuberculosis Complex Rather than Para-Aminosalicylic Acid Resistanceen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalAntimicrobial Agents and Chemotherapyen
dc.identifier.pmcidPMC2976163en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionMolecular Mycobacteriology, Research Center Borstel, Borstel, Germanyen
dc.contributor.institutionDepartment of Genetics, University of Cambridge, Cambridge, United Kingdomen
dc.contributor.institutionNational Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germanyen
kaust.authorArcher, John A.C.en

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