Biological cost in Mycobacterium tuberculosis with mutations in the rpsL, rrs, rpoB, and katG genes

Spies, Fernanda Sá; Groll, Andrea Von; Ribeiro, Andrezza Wolowski; Soares, Daniela Fernandes Ramos; Ribeiro, Marta Osório; Costa, Elis Regina Dalla; Martin, Anandi; Palomino, Juan Carlos; Rossetti, Maria Lucia; Zaha, Arnaldo; Silva, Pedro Eduardo Almeida da


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.

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