Streptococcus suis (S. suis) is an emerging zoonotic agent that is responsible for significant economic losses to the porcine industry worldwide. However, most research regarding the pathogenic mechanisms has used in vitro cultures of S. suis, which may not provide an accurate representation of the in vivo biological activities. In this study, 188 differential abundance S. suis proteins were identified in in vivo samples obtained from the blood of the infected pigs. These were compared with in vitro samples by a Tandem Mass Tags (TMT) experiment. Thus, a virulence associated network was established using the enriched differential abundance proteins (obtained via bioinformatics analysis in this study) and the previously reported putative virulence factors associated with in vivo infection. One of the most important up-regulated hubs in this network, adhE (an acetaldehyde-CoA/alcohol dehydrogenase) was found. Furthermore, knocking out adhE in S. suis serotype 2 strain ZY05719 decreased virulence. Cell culture experiments and far-western blot analysis showed that adhE is involved in adhesion to Caco-2 cells; Hsp60 could be one of the receptors for this protein.
Significance: This study is a systematical research to identify in vivo regulated virulence associated proteins of S. suis in pigs. It constructs a network consisting of in vivo infection related factors for the first time to get to know the coordinated actions of a multitude of factors that lead to host pathogenicity and filter the most important hubs. The individual factors that contribute to infection is also identified. A novel differential protein adhE which is one of the most important hubs of this network and is up-regulated in abundance in vivo is found to moonlight as an important adhesion by binding Hsp60 and finally contributes to virulence.
Keywords: Comparative proteomics; In vivo; Streptococcus suis serotype 2; Virulence; adhE.
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