Synergistic Mechanism between Influenza A Virus and Streptococcus pneumoniae in pnemocytes

Parana

Encuentro; LIV Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2018

SAIB

Influenza A Virus (IAV) and Streptococcus pneumoniae (Spn) are considered as two of the most important human pathogens. Co-infections withboth microorganisms usually lead to severe respiratory disease, and occasionally, death. Although it has been described a clear synergismbetween these two pathogens, the mechanism of how they interact during infection of eukaryotic cells is poorly understood. We set up a coinfectionmodel using A549 pneumocyte cells, and we observed that when cells were previously infected with IAV, the intracellular survival ofSpn duplicated in comparison with non-IAV-infected cells. It has been reported that Spn can be eliminated by the autophagic pathway inpneumocytes. Our hypothesis was that the increased Spn survival in IAV-infected cells is due to a blockage of the autophagosome/lysosomefusion caused by the viral M2 protein. This was confirmed by over-expression of M2 in A549 cells, where we observed an increased Spnsurvival. In addition to this host factor, we also proposed that Spn should sense IAV-induced changes at intracellular level in pneumocytes toincrease its survival, and these changes should be sensed by a two-component system (TCS) to induce a bacterial response to these stressconditions. We screened TCS mutants and we found that the ΔvisRH did not increase its survival as wt cells. An RNAseq analysis revealed thatVisRH regulates the expression of many genes that are involved in the acidic/oxidative stress response. Taken together, these results contributeto elucidate the Spn survival mechanism in IAV-infected pneumocytes.