Fagunloye, O. G. | bioRxiv Science

bioRxiv2025

Siglec homologs interact with membrane-bound Heat Shock Protein 70 (Hsp70) during early infection of the Schistosoma mansoni susceptible (BB02) Biomphalaria glabrata snail host.

Sialic acid-binding immunoglobulin-like lectins (siglecs) are cell surface receptors involved in immune signaling. When Schistosoma mansoni infects its intermediate host, the Biomphalaria glabrata snail, early stress responses, such as upregulation of heat shock protein 70 (Hsp70) are observed. We hypothesized that stress-induced Hsp70 translocates to the cell membrane and interacts with siglec homologs to modulate immune responses in the snail. Utilizing in-silico approaches, we identified B. glabrata transcripts homologous to human and molluscan siglecs, followed by homology modeling and molecular docking, which predicted a salt bridge between glutamic acid 479 on BgHsp70 and lysine 47 on a siglec homolog (BgPrx), suggesting a plausible binding interface. To validate this, we performed real-time qPCR from infected susceptible juvenile BB02 snails, revealing significant upregulation of siglec homolog transcripts shortly after infection. Additionally, protein fractionation and immunocytochemistry confirmed BgHsp70 localization to the membrane post-infection. These results support a model in which siglec-Hsp70 interactions may dampen stress signaling to suppress host immune defenses. Concurrently, S. mansoni employs glycan mimicry, presenting host-like sialylated structures that likely engage siglecs and further misdirect the immune response. Together, our findings suggest that BgHsp70-siglec interactions, in combination with parasite glycan mimicry, constitute a potential immune evasion mechanism enabling schistosome establishment in susceptible B. glabrata snails.

microbiology↗

bioRxiv2022

Wall teichoic acids facilitate the release of toxins from the surface of Staphylococcus aureus.

A major feature of the pathogenicity of Staphylococcus aureus is its ability to secrete cytolytic toxins. This process involves the translocation of the toxins from the cytoplasm, through the bacterial membrane and the cell wall to the external environment. The process of their movement through the membrane is relatively well defined, involving both general and toxin-specific secretory systems. Movement of the toxins through the cell wall was considered to involve the passive diffusion of the proteins through the porous cell wall structures, however, recent work suggests that this is more complex, and here we demonstrate a role for the wall teichoic acids (WTA) in this process. Utilising a genome-wide association approach we identified a polymorphism in the locus encoding the WTA biosynthetic machinery as associated with the cytolytic activity of the bacteria. We verified this association using an isogenic mutant set and found that WTA is required for the release of several cytolytic toxins from the bacterial cells. We show this effect is mediated by a change in the electrostatic charge across the cell envelope that results from the loss of WTA. As a major target for the development of novel therapeutics, it is important that we fully understand the entire process of cytolytic toxin production and release. These findings open up a new aspect to this process that requires in-depth investigation, while also demonstrating that clinical isolates can utilise WTA production to vary their cytotoxicity, thereby altering their pathogenic capabilities. ImportanceThe production and release of cytolytic toxins is a critical aspect to the pathogenicity of many bacterial pathogens. In this study we demonstrate a role for wall teichoic acids, molecules that are anchored to the peptidoglycan of the bacterial cell wall, in the release of toxins from S. aueus cells into the extracellular environment. Our findings suggest this effect is mediated by a gradient of electrostatic charge the presence of the negatively charged WTA molecules create across the cell envelope. This work brings an entirely new aspect to our understanding of the cytotoxicity of S. aureus and demonstrates a further means by which this major human pathogen can adapt its pathogenic capabilities.

microbiology↗