<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Vanessa Mathys</style></author><author><style face="normal" font="default" size="100%">Wintjens, René</style></author><author><style face="normal" font="default" size="100%">Lefèvre, Philippe</style></author><author><style face="normal" font="default" size="100%">Bertout, Julie</style></author><author><style face="normal" font="default" size="100%">Singhal, Amit</style></author><author><style face="normal" font="default" size="100%">Kiass, Mehdi</style></author><author><style face="normal" font="default" size="100%">Kurepina, Natalia</style></author><author><style face="normal" font="default" size="100%">Wang, Xiao-Ming</style></author><author><style face="normal" font="default" size="100%">Mathema, Barun</style></author><author><style face="normal" font="default" size="100%">Baulard, Alain</style></author><author><style face="normal" font="default" size="100%">Kreiswirth, Barry N</style></author><author><style face="normal" font="default" size="100%">Bifani, Pablo</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Molecular genetics of para-aminosalicylic acid resistance in clinical isolates and spontaneous mutants of Mycobacterium tuberculosis.</style></title><secondary-title><style face="normal" font="default" size="100%">Antimicrob Agents Chemother</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Antimicrob. Agents Chemother.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Aminosalicylic Acid</style></keyword><keyword><style  face="normal" font="default" size="100%">Antitubercular Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Bacterial Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Drug Resistance, Bacterial</style></keyword><keyword><style  face="normal" font="default" size="100%">Folic Acid</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Microbial Sensitivity Tests</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Mycobacterium tuberculosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Structure-Activity Relationship</style></keyword><keyword><style  face="normal" font="default" size="100%">Thymidylate Synthase</style></keyword><keyword><style  face="normal" font="default" size="100%">Thymine</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2009</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2009 May</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">53</style></volume><pages><style face="normal" font="default" size="100%">2100-9</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The emergence of Mycobacterium tuberculosis resistant to first-line antibiotics has renewed interest in second-line antitubercular agents. Here, we aimed to extend our understanding of the mechanisms underlying para-aminosalicylic acid (PAS) resistance by analysis of six genes of the folate metabolic pathway and biosynthesis of thymine nucleotides (thyA, dfrA, folC, folP1, folP2, and thyX) and three N-acetyltransferase genes [nhoA, aac(1), and aac(2)] among PAS-resistant clinical isolates and spontaneous mutants. Mutations in thyA were identified in only 37% of the clinical isolates and spontaneous mutants. Overall, 24 distinct mutations were identified in the thyA gene and 3 in the dfrA coding region. Based on structural bioinformatics techniques, the altered ThyA proteins were predicted to generate an unfolded or dysfunctional polypeptide. The MIC was determined by Bactec/Alert and dilution assay. Sixty-three percent of the PAS-resistant isolates had no mutations in the nine genes considered in this study, revealing that PAS resistance in M. tuberculosis involves mechanisms or targets other than those pertaining to the biosynthesis of thymine nucleotides. The alternative mechanism(s) or pathway(s) associated with PAS resistance appears to be PAS concentration dependent, in marked contrast to thyA-mutated PAS-resistant isolates.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/19237648?dopt=Abstract</style></custom1></record></records></xml>