Viral co-infection replaces effects of suilysin on adherence and invasion of Streptococcus suis into respiratory epithelial cells grown under air-liquid interface conditions.

Meng, Fandan; Tong, Jie; Vötsch, Désirée; Peng, Ju-Yi; Cai, Xuehui; Willenborg, Maren; Herrler, Georg; Wu, Naihuei; Valentin-Weigand, Peter

Streptococcus suis is an important zoonotic pathogen, which can infect humans and pigs worldwide, posing a potential risk to global public health. Suilysin, a pore-forming cholesterol-dependent cytolysin, is considered to play an important role in the pathogenesis of S. suis infections. It is known that infection with influenza A viruses may favor the susceptibility to secondary bacterial infection resulting in more severe disease and increased mortality. However, the molecular mechanisms underlying these co-infections are incompletely understood. Applying highly differentiated primary porcine respiratory epithelial cells grown under air-liquid interface (ALI) conditions, we analyzed the contribution of swine influenza viruses (SIV) to the virulence of S. suis with a special focus on its cytolytic toxin suilysin. We found that during secondary bacterial infection, suilysin of S. suis contributes to the damage of well-differentiated respiratory epithelial cells in the early stage of infection, whereas cytotoxic effects induced by SIV became prominent at later stages of infection. Prior infection by SIV enhanced the adherence to and colonization of porcine airway epithelial cells by the wildtype S. suis strain (wt) and a suilysin-negative S. suis mutant in a sialic-acid dependent manner. A striking difference was observed with respect to bacterial invasion. After bacterial mono-infection, only wt S. suis showed an invasive phenotype whereas the mutant remained adherent. When the epithelial cells were pre-infected with SIV, also the suilysin-negative mutant showed invasion capacity. Therefore, we propose that co-infection with SIV may compensate for the lack of suilysin in the adherence and invasion process of suilysin-negative S. suis.