Capsular Sialic Acid of Streptococcus suis Serotype 2 Binds to Swine Influenza Virus and Enhances Bacterial Interactions with Virus-Infected Tracheal Epithelial Cells

Abstract

bStreptococcus suis serotype 2 is an important swine bacterial pathogen, and it is also an emerging zoonotic agent. It is unknown how S. suis virulent strains, which are usually found in low quantities in pig tonsils, manage to cross the first host defense lines to initiate systemic disease. Influenza virus produces a contagious infection in pigs which is frequently complicated by bacterial coinfections, leading to significant economic impacts. In this study, the effect of a preceding swine influenza H1N1 virus (swH1N1) infection of swine tracheal epithelial cells (NTPr) on the ability of S. suis serotype 2 to adhere to, invade, and activate these cells was evaluated. Cells preinfected with swH1N1 showed bacterial adhesion and invasion levels that were increased more than 100-fold compared to those of normal cells. Inhibition studies confirmed that the capsular sialic acid moiety is responsible for the binding to virus-infected cell surfaces. Also, preincubation of S. suis with swH1N1 significantly increased bacterial adhesion to/invasion of epithelial cells, suggesting that S. suis also uses swH1N1 as a vehicle to invade epithelial cells when the two infections occur simultaneously. Influenza virus infection may facilitate the transient passage of S. suis at the respiratory tract to reach the bloodstream and cause bacteremia and septicemia. S. suis may also increase the local inflammation at the respiratory tract during influenza infection, as suggested by an exacerbated expression of proinflammatory mediators in coinfected cells. These results give new insight into the complex interactions between influenza virus and S. suis in a coinfection model.

Dynamic Virus-Bacterium Interactions in a Porcine Precision-Cut Lung Slice Coinfection Model: Swine Influenza Virus Paves the Way for Streptococcus suis Infection in a Two-Step Process

“…In agreement with previous results (13,16) but in contrast to findings by Wang et al using new-born pig tracheal cells (25), attachment of S. suis to PCLS was facilitated by suilysin. Most interestingly, we found that the encapsulated strain was as adherent as the unencapsulated mutant, which differs from what we and others have observed using conventional immortalized monolayer cell culture systems (12,13,25). Notably, we observed different adherence patterns of the encapsulated S. suis strain, which adhered homogenously to all cell types, and the unencapsulated mutant strain, which showed a cluster-like adherence, preferentially to mucus.…”

“…Recently it has been reported that influenza virus enhances pneumococcal colonization and growth in the upper respiratory tract (27) and that, vice versa, coinfection with Streptococcus pneumoniae complicates influenza-induced pneumonia (28). For S. suis it has been shown that preinfection of a porcine tracheal epithelial cell line with swine influenza virus (SIV) increased bacterial adherence and invasion (25). To investigate possible effects of SIV on S. suis adherence and colonization in a model that is closer to the in vivo situation, we used the PCLS model and preinfected slices with SIV followed by infection with S. suis strain 10 or the unencapsulated mutant strain 10cps⌬EF.…”

“…Since previous in vitro studies using immortalized epithelial cell lines had shown that nonencapsulated S. suis strains adhered (and invaded) more efficiently than encapsulated strains (12,13,25), we included the capsule-deficient mutant strain 10cps⌬EF in our studies. In contrast to previous findings with conventional monolayer cell cultures, the adherence levels of the encapsulated wt strain and its unencapsulated mutant were nearly equal ( Fig.…”

“…Porcine PCLS have not yet been used for viral-bacterial coinfections. Few studies on coinfections of SIV and S. suis have been published recently (25,31,32), but these were performed with NPTr cells, an immortalized porcine tracheal cell line, which limits conclusions on the in vivo situation.…”

Sialic acid-dependent interactions between influenza viruses and Streptococcus suis affect the infection of porcine tracheal cells

“…In this way, the bacteria may indirectly affect infection by other pathogens like influenza viruses. A direct interaction between influenza viruses and streptococci has recently been reported for SIV (H1N1 subtype) and Streptococcus suis serotype 2 (Wang et al, 2013). This is a highly virulent serotype of Streptococcus suis in swine and in addition has a zoonotic potential as indicated by occasional epidemics in humans (Feng et al, 2014).…”