Synergistic Mechanism between Influenza A virus and Streptococcus pneumoniae in pneumocytes

CORTES, PAULO R.; PEREZ, DANIEL R.; OLIVERO , NADIA; HERNANDEZ MORFA, MIRELYS; REINOSO VIZCAÍNO, NICOLÁS MARTÍN; YANDAR BARAHONA, NUBIA Y.; ECHENIQUE, JOSÉ

Paraná

Congreso; LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2019

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 coinfection model 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 ∆visRH 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.