Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-10-15
pubmed:abstractText
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.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-11896268, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-12519922, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-14759262, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-15225321, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-17005759, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-17192416, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-17987113, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-18070553, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-18550737, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-18551748, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-19020060, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-19237648, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-19890396, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-20427375, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-20457747, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-2231712, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-8381814, http://linkedlifedata.com/resource/pubmed/commentcorrection/20805400-9157152
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1098-6596
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4794-8
pubmed:dateRevised
2011-7-28
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Thr202Ala in thyA is a marker for the Latin American Mediterranean lineage of the Mycobacterium tuberculosis complex rather than para-aminosalicylic acid resistance.
pubmed:affiliation
Molecular Mycobacteriology, Research Center Borstel, Parkallee 1, Borstel, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't