Decyphering Mycobacterium tuberculosis host specificity through the integration of genomics and infection biology

Autor: Santamaria, Guillem, Renau-Mínguez, Chantal, Gomis, Carlos, Espert, Antonio, Buksa, Nikolina, Ruiz-Rodríguez, Paula, Pinto, Filipe, Coscollá, Mireia
Rok vydání: 2021
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
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Popis: Resumen del póster presentado al 41st Annual Congress of the European Society of Mycobacteriology (ESM), celebrado de forma virtual del 28 al 29 de junio de 2019.
Mycobacterium tuberculosis is the microorganism that produces tuberculosis, which is among the top 10 causes of death worldwide. Most of its lineages infect predominantly humans, except for four, which infect a wide range of other mammals. We will refer to them as animal-associated lineages. As understanding the genetic basis of host specificity can inform about the virulence factors of M. tuberculosis in each host, our objective is to decipher if host specificity correlates with virulence in vitro, and with lineage specific genomic signatures. We combined experiments in macrophage infection model with whole genome sequencing analysis of ~35.000 clinical M. tuberculosis strains to determine genomic specific signatures of the bacteria during the infectious process. We observed different genomic signatures between human and animal M. tuberculosis associated lineages. A differential signature was observed in three of the four genes that encode for phospholipase C in M. tuberculosis (plcABC) and PPE38. These genes are part of a previously described Region of Difference (RD), RD5, which is unevenly distributed between animal- and human-associated lineages. This region is completely lost in two and partially lost in one out of four of the animal lineages, while present in most of the isolates belonging to the human-associated lineages. Phylogenomic analysis showed that these deletions happened several times during evolution indicating the loss of these regions could be under differential selection pressure in animal- and human-associated strains. Because phospholipase C has been previously linked to M. tuberculosis virulence, we explored the differential expression of these genes between lineages infecting macrophages coming from different hosts.
Databáze: OpenAIRE
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