IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Fitness of multidrug-resistant Mycobacterium tuberculosis clinical isolates assessed by axenic and intracellular competition, and activation of macrophage effector mechanisms
Autor/es:
VIVIANA RITACCO; NOEMÍ YOKOBORI; MARÍA DEL CARMEN SASIAIN; BEATRIZ LÓPEZ
Lugar:
Vancouver
Reunión:
Simposio; Keystone Symposia - New Developments in Our Basic Understanding of Tuberculosis; 2017
Institución organizadora:
Keystone Symposia
Resumen:
Emergence of transmissible MDR tuberculosis is a major threat to global health. In Argentina the M strain of Mycobacterium tuberculosis, managed to persist in the community for four decades1 and caused the largest MDR tuberculosis outbreak in Latin America2. Some degree of intra-strain variability also emerged, including non-prosperous genotypes closely related to M. This was the case of strain 410, which caused a single case in two decades. Bacterial fitness is of multifaceted nature, and there is no consensus on the parameters best reflecting it. We hypothesize that the epidemiological success of the M strain stems from its enhanced fitness. Methods: H37Rv, isolates 6548 and 15526 of the M strain and the 410 strain were evaluated by: i) Competition assays in axenic cultures and inside human macrophages where strains were differentiated by counting colony forming units (CFU) in plates with and without drugs. ii) Resistance to macrophage effector mechanisms activated by IFN-, vitamin D3 and their combination, and induction of apoptosis with staurosporin. Results: i) in axenic conditions, both isolates of the M strain outgrowed the 410 strain; no differences were observed in intracellular competition. ii) Treatment with staurosporin significantly reduced 410 CFUs. Despite variability among subjects, our results suggest that resistance of the 410 strain to activation by IFN- and IFN-+Vitamin D3 is compromised. However, CFUs for isolate 15526 were also reduced in the latter assay. Collectively, our results suggest that the 410 strain is less fit than the outbreak M isolates. Outcomes of the different fitness assays are discussed.References1. Eldholm et. al., 2015 (10.1038/ncomms8119)2. Ritacco et. al., 2011 (10.1016/j.meegid.2011.06.006) FundingFundación Roemmers and ANPCyT, Argentina.