Streptococcus suis infection: An emerging/reemerging challenge of bacterial infectious diseases?

Feng, Youjun; Zhang, Huimin; Wu, Zuowei; Wang, Shihua; Cao, Min; Hu, Dan; Wang, Changjun

With the exceptions of neuB and neuC, the remaining six among the eight enzymes proposed by Wilson 100 NeuB is a sialic acid synthase that catalyzes the last committed step of the de novo biosynthetic pathway of sialic acid, a major element of bacterial surface structure. Recently, we systematically addressed its molecular and immunological role in bacterial virulence and claimed that an altered architecture of S. suis surface attenuates its virulence. 100, 141 Similarly, neuC that encodes UDP N-Acetylglucosamine 2-Epimerase with an involvement in sialic acid biosynthesis is also found to be essential for capsule production and required for virulence in a mouse infection model. 142 Gdh, the glutamine dehydrogenase-encoding gene, was originally known as a virulence factor. It has been widely applied 128 Si et al. 127 demonstrated that glutamine synthetase, the glnA-encoding product, is associated with S. suis virulence using a mouse model. We and two other research groups 96, 129, 143 have reported that S. suis enolase acts as an octamer, 144 and can exported to the bacterial surface with capability of binding to host fibronectin, indicating its possible role in crosstalk between pathogen and host. However, the protective efficiency of recombinant enolase with different bacterial origins does not seem consistent. 96, 129, 130 Similarly, the gene encoding Inosine 5-monophosphate dehydrogenase, a nucleotide metabolism-related enzyme, was initially cloned by Lu's research group, and was subsequently suggested to be involved in full virulence of SS2-H, a Chinese strain in the infection model of piglets. 131 Modification of the bacterial surface is critical for successful invasion and entry of pathogens into host cells. Gottschalk's group systemically evaluated contributions of two kinds of modification systems to S. suis pathogenicity: lipoteichoic acid (LTA)-d-alanylation, and peptidoglycan (PG) N-deacetylation, respectively. 132, 133 The ΔdltA mutant with defection in LTA d-alanylation was found to be attenuated in its virulence, which can be correlated with its diminished adherence/invasion of porcine brain microvascular endothelial cells, and decreased capacity to escape immune clearance or killing by porcine neutrophils. 132 Fittipaldi et al. 133 observed that the expression level of the pgdA gene can be induced upon interaction of SS2 with neutrophils in vitro and infected mice in vivo, implying that PG N-deacetylation is tightly involved in SS2 infections. This hypothesis was further validated by virulence attenuation of the ΔpgdA mutant of SS2. Not only does ApuA behave like a bacterial surface protein with a LPKTGE cell-wall-anchoring motif at C-terminus, but it also functions as a bi-functional amylopullulanase. 134 Further genetic study showed that the multifunctional α-glucan-degrading enzyme ApuA can promote adhesion to porcine epithelium and mucus, which might link bacterial carbohydrate utilization to its capability of colonization and invasiveness into hosts. We and the other research group demonstrated that Sortase A (SrtA, originally referred to as a transpeptidase in Staphylococcus aureus) is essential for full virulence of SS2. 136, 137 However, other sortase paralogs SrtBCD are not associated with bacterial virulence. 145 In addition, we reported the functional definition of di-peptidyl peptidase IV (DPP IV) in S. suis 2, and also confirmed that it does contribute greatly to bacterial virulence. 135 Quorum sensing is a m