Streptococcus suis Uptakes Carbohydrate Source from Host Glycoproteins by N-glycans Degradation System for Optimal Survival and Full Virulence during Infection

Abstract

Infection with the epidemic virulent strain of Streptococcus suis serotype 2 (SS2) can cause septicemia in swine and humans, leading to pneumonia, meningitis and even cytokine storm of Streptococcal toxic shock-like syndrome. Despite some progress concerning the contribution of bacterial adhesion, biofilm, toxicity and stress response to the SS2 systemic infection, the precise mechanism underlying bacterial survival and growth within the host bloodstream remains elusive. Here, we reported the SS2 virulent strains with a more than 20 kb endoSS-related insertion region that showed significantly higher proliferative ability in swine serum than low-virulent strains. Further study identified a complete N-glycans degradation system encoded within this insertion region, and found that both GH92 and EndoSS contribute to bacterial virulence, but that only DndoSS was required for optimal growth of SS2 in host serum. The supplement of hydrolyzed high-mannose-containing glycoprotein by GH92 and EndoSS could completely restore the growth deficiency of endoSS deletion mutant in swine serum. EndoSS only hydrolyzed a part of the model glycoprotein RNase B with high-mannose N-linked glycoforms into a low molecular weight form, and the solo activity of GH92 could not show any changes comparing with the blank control in SDS-PAGE gel. However, complete hydrolyzation was observed under the co-incubation of EndoSS and GH92, suggesting GH92 may degrade the high-mannose arms of N-glycans to generate a substrate for EndoSS. In summary, these findings provide compelling evidences that EndoSS-related N-glycans degradation system may enable SS2 to adapt to host serum-specific availability of carbon sources from glycoforms, and be required for optimal colonization and full virulence during systemic infection.

Streptococcus suis Research: Progress and Challenges

“…To survive and even proliferate in host blood, S. suis must mainly overcome the innate immunity and nutritional limitations in this host compartment [24]. Ma et al [31] found that S. suis serotype 2 virulent strains with higher proliferative ability in swine serum than low-virulent strains, possess a >20 kb endoSS-related insertion region. Further analyses identified a complete N-glycans' degradation system encoded within this insertion region.…”

Comparative genomic analyses provide clues to capsule switch inStreptococcus suis

“…However, ST25 (CC29) and ST28 (CC28), accounting for larger proportions of SS2 strains in North American, present less virulence potentials in animal model (Athey et al, 2015; Fittipaldi et al, 2011). In accordance, ST28 strains in China are also regard as representive avirulent strains (Guo et al, 2020; Ma et al, 2020; Wang et al, 2017). Those reports suggested that CC28 and CC29 SS2, which are phylogenetically distinct from CC1 SS2, are the pool of strains with lower virulence levels.…”

A Fluorogenic Disaccharide Substrate for α-Mannosidases Enables High-Throughput Screening and Identification of an Inhibitor of the GH92 Virulence Factor from Streptococcus pneumoniae

“…This greater reduction in virulence may stem from the SpGH92-mediated trimming of α-1,2 linkages from high-mannose-containing N -glycans being a prerequisite for the release of N -glycans by EndoD (Figure A) . Similarly, deletion of the gene encoding GH92 in Streptococcus suis SS2 revealed its contribution to virulence, supporting a general role for N -glycan processing as a virulence mechanism in pathogenic streptococci, a large proportion of which possess genes encoding GH92 enzymes . Accordingly, small-molecule inhibitors of SpGH92 may ultimately serve to deliver antivirulence therapeutics that target S. pneumoniae and possibly other streptococci.…”