title: Biological cost in Mycobacterium tuberculosis with mutations in the rpsL, rrs, rpoB, and katG genes.
abstract: When bacteria develop drug-resistant mutations, there is often an associated biological cost; however, some strains can exhibit low- or no-cost mutations. In the present study, a quantitative resazurin reduction assay was used to measure the biological cost of Mycobacterium tuberculosis isolates that contained different mutations in the rpsL, rrs, rpoB, and katG genes, and showed different resistance profiles. Biological costs were determined by comparing the growth curves of drug-resistant isolates with drug-susceptible strains. Some strains, such as those with rpoB mutations other than S531L and strains with mutations in all of the studied genes, grew more slowly than did drug-susceptible strains. However, some strains grew more quickly than drug-susceptible strains, such as those that had only the rpsL K43R mutation. Strains with the mutation katG S315T presented heterogeneous biological costs. When analyzed individually, strains with the mutations rpsL43/katG315, rpoB531, and rpoB531/katG315 grew faster than drug-susceptible strains. The results suggest that some strains with the most common mutations correlated to a high resistance toward streptomycin, isoniazid and rifampicin can grow as well as or better than susceptible strains.
authors.affiliation: Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. nandaspies@gmail.com
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Spies
authors.forename: Andrea
authors.initials: A
authors.lastname: von Groll
authors.forename: Andrezza W
authors.initials: AW
authors.lastname: Ribeiro
authors.forename: Daniela F
authors.initials: DF
authors.lastname: Ramos
authors.forename: Marta O
authors.initials: MO
authors.lastname: Ribeiro
authors.forename: Elis Regina
authors.initials: ER
authors.lastname: Dalla Costa
authors.forename: Anandi
authors.initials: A
authors.lastname: Martin
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Palomino
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Rossetti
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Zaha
authors.forename: Pedro Eduardo A
authors.initials: PE
authors.lastname: da Silva
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D002374:Catalase / Q000235:genetics; D012321:DNA-Directed RNA Polymerases; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D012336:RNA, Ribosomal, 16S; D012269:Ribosomal Proteins; C034212:ribosomal protein S12; C505805:rpoB protein, Mycobacterium tuberculosis; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases