YSIRK-G/S-directed translocation is required for Streptococcus suis to deliver diverse cell wall anchoring effectors contributing to bacterial pathogenicity

Abstract

The Streptococcus suis serotype 2 (SS2) is a significant zoonotic pathogen that is responsible for various swine diseases, even causing cytokine storms of Streptococcal toxic shock-like syndromes amongst human. Cell wall anchoring proteins with a C-terminal LPxTG are considered to play vital roles during SS2 infection; however, their exporting mechanism across cytoplasmic membranes has remained vague. This study found that YSIRK-G/S was involved in the exportation of LPxTGanchoring virulence factors MRP and SspA in virulent SS2 strain ZY05719. The whole-genome analysis indicated that diverse LPxTG proteins fused with an N-terminal YSIRK-G/S motif are encoded in strain ZY05719. Two novel LPxTG proteins SspB and YzpA were verified to be exported via a putative transport system that was dependent on the YSIRK-G/S directed translocation, and portrayed vital functions during the infection of SS2 strain ZY05719. Instead of exhibiting an inactivation of C5a peptidase in SspB, another LPxTG protein with an N-terminal YSIRK-G/S motif from Streptococcus agalactiae was depicted to cleave the C5a component of the host complement. The consequent domain-architecture retrieval determined more than 10,000 SspB/YzpA like proteins that are extensively distributed in the Gram-positive bacteria, and most of them harbor diverse glycosyl hydrolase or peptidase domains within their middle regions, thus presenting their capability to interact with host cells. The said findings provide compelling evidence that LPxTG proteins with an N-terminal YSIRK-G/S motif are polymorphic effectors secreted by Gram-positive bacteria, which can be further proposed to define as cell wall anchoring effectors in a new subset.

Bap-Independent Biofilm Formation in Staphylococcus xylosus

“…Proteins containing a YSIRK signal peptide and an LPxTG cell anchor motif have been discussed in different contexts in the past and different functions including peptidase and hydrolase activity have been assigned to those proteins [36,37]. Furthermore, Bhp, a Bap homolog found in S. epidermidis, has been speculated to mediate biofilm formation at first [11]; however, disruption of bhp did not result in any biofilm reduced phenotypes [38].…”

Spatial regulation of protein A in Staphylococcus aureus

“…The LysM domain is present in other cell wall anchored YSIRK/GXXS proteins as well. In a recent study, Bai et al analyzed over 10,000 YSIRK/GXXS proteins from different bacterial species and the LysM domain is found in 0.29% of YSIRK/GXXS proteins containing glycosyl hydrolase domains (Bai et al., 2020). Besides the LysM domain, other cell wall‐binding domains, such as GW, SH3 domains, can also be found in the YSIRK/GXXS family proteins (Pfam: PF04650).…”

Host PTX3 Protein and Bacterial Capsule Coordinately Regulate the Inflammatory Response during Streptococcus suis Infection

“…Mouse infection assays were performed as previously reported [ 29 ]. Mice were intraperitoneally injected with HA9801 3 × 10 8 CFU/mouse with or without PTX3 (5 μg, 10 μg and 20 μg, respectively).…”