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Unraveling host-specific in vitro virulence profiles of Mycobacterium tuberculosis ecotypes

M Caballer-Gual(1) P Ruiz-Rodriguez(1) G Santamaria(1) H Hiza(1) M Coscolla(1)

1:Universidad de València

Tuberculosis is caused by the Mycobacterium tuberculosis complex (MTBC), which encompasses 13 distinct lineages or ecotypes. Despite sharing a genetic similarity of over 99%, these ecotypes demonstrate differential host preference, distinguishing between human and animal-associated lineages. Understanding host-pathogen interactions and their compatibility will allow us to decipher the factors that influence M. tuberculosis virulence.

Our study hypothesizes that the degree of host compatibility influences the virulence potential of M. tuberculosis strains, with increased virulence observed when strains infect their preferred hosts. To investigate this hypothesis, we employed an in vitro infection model using human and bovine macrophages (THP1 and BoMac cells) infected with two human-associated M. tuberculosis strains belonging to lineages L5 and L6, as well as two strains associated with animals: Mycobacterium bovis of lineage A4 and Chimpanzee bacillus from the A1 lineage.

Our findings support our hypothesis, revealing an augmented infection ratio in host cells when infected with their preferred strain. Interestingly, our investigation reveals distinct cellular responses across different host-pathogen combinations. Specifically, less compatible combinations exhibited higher cell viability, suggesting potential compromises in host defense mechanisms facilitating enhanced cell survival despite infection. Conversely, more compatible combinations demonstrated elevated levels of apoptotic cells, indicative of a heightened immune response aimed at restricting the infection.

These results underscore the interplay between host compatibility and M. tuberculosis virulence, highlighting the importance of host-pathogen interactions in shaping disease outcomes. A comprehensive understanding of these interactions holds promise for the development of targeted therapeutic strategies against tuberculosis

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