Assessment of nutrient starvation-driven stress as part of a multifaceted approach to analyze the fitness of a highly successful MDR strain of Mycobacterium tuberculosis (Resumen aprobado)

RITACCO V; WAINMAYER I; LÓPEZ B; SIMBOLI N; MONTESERIN J; SASIAIN M; PAUL R; N YOKOBORI

Buenos Aires

Congreso; 18th International Congress on Infectious Diseases; 2018

International Society for Infectious Diseases

The M strain of Mycobacterium tuberculosis caused the largest MDR tuberculosis outbreak in Latin America and we hypothesized that its epidemiological success relies on its biological traits. Bacterial fitness assessment is complex and no single parameter can predict the success of a certain pathogen. Table 1 schematically synthesizes our previous results on performance of an early M strain representative (isolate 6548) and the non-prosperous variant 410 in various fitness assays. Despite the poor axenic growth of the M strain, its overall performance was remarkable.Table 1M strain (6548)410 variantAxenic culture lag phase++++Axenic culture replication rate++++Resistance to drug-driven stress++++Growth in axenic competition++++Mouse survival++++Mouse granuloma formation++++rpoB mutationS450LH445LRifampicin-resistant mutants with substitutions in rpoB codon 445 are assumed to be less fit, and an enhanced susceptibility to nutrient starvation has been reported (10.2217/fmb-2017-0022). Herein, a nutrient starvation assay was performed to further compare the fitness of two M outbreak representatives with that of the non-prosperous variant 410.The reference strain H37Rv, M isolates 6548 and 15526 and 410 variant were cultured in triplicate at 37ºC for 28 and 56 days in PBS-0.05% Tween-80. CFUs/ml were determined by serial dilution and plating in 7H11-AD agar plates.Table 2 shows that the 410 variant was highly susceptible to starvation (Student?s t-test *P