Streptococcus pneumoniae Cell Wall-Localized Trigger Factor Elicits a Protective Immune Response and Contributes to Bacterial Adhesion to the Host

Abstract

Trigger factor (TF) has a known cytoplasmic function as a chaperone. In a previous study we showed that pneumococcal TF is also cell-wall localized and this finding combined with the immunogenic characteristic of TF, has led us to determine the vaccine potential of TF and decipher its involvement in pneumococcal pathogenesis. Bioinformatic analysis revealed that TF is conserved among pneumococci and has no human homologue. Immunization of mice with recombinant (r)TF elicited a protective immune response against a pneumococcal challenge, suggesting that TF contributes to pneumococcal pathogenesis. Indeed, rTF and an anti-rTF antiserum inhibited bacterial adhesion to human lung derived epithelial cells, indicating that TF contributes to the bacterial adhesion to the host. Moreover, bacteria lacking TF demonstrated reduced adhesion, in vitro, to lung-derived epithelial cells, neural cells and glial cells. The reduced adhesion could be restored by chromosomal complementation. Furthermore, bacteria lacking TF demonstrated significantly reduced virulence in a mouse model. Taken together, the ability of rTF to elicit a protective immune response, involvement of TF in bacterial adhesion, conservation of the protein among pneumococcal strains and the lack of human homologue, all suggest that rTF can be considered as a future candidate vaccine with a much broader coverage as compared to the currently available pneumococcal vaccines.

Whole-genome analysis of probiotic product isolates reveals the presence of genes related to antimicrobial resistance, virulence factors, and toxic metabolites, posing potential health risks

“…VFs related to capsule or biofilm formation and bacterial adherence were detected in the genome of S. thermophilus TK-P3A, which also be reported to facilitate probiotic survival in gastrointestinal tract by strengthening acid resistance and intestinal colonization [ 17 , 24 – 30 ]. More research needs to clarify the underlying mechanisms of adaption and pathogenicity.…”

Streptococcus pneumoniae inhibits purinergic signaling and promotes purinergic receptor P2Y2 internalization in alveolar epithelial cells

“…A serial dilution was generated and plated on agar for each new lot to determine the bacterial concentration. For each experiment, a new aliquot of bacteria was slowly thawed and added to the supernatant of the cells at an MOI of 100 as described in the literature (65)(66)(67)(68). Cells were incubated at 37°C in a 5% CO 2 atmosphere for 2 h and then subjected to further experiments.…”

Identification of conditionally essential genes for Streptococcus suis infection in pigs

“…The gene encoding the chaperone DnaJ of S. suis was shown to contribute to thermotolerance [56], whereas in S. pneumoniae, DnaJ was shown to play an important role in inflammatory responses [57]. Trigger factor, another chaperone with peptidyl-prolyl cis-trans isomerization that assists proteins in its proper folding and maturation [58], was shown to contribute to stress tolerance and alter the expression of genes involved in virulence in S. suis [59] and other pathogenic streptococci [60]. Besides assisting in stress responses, a role in adhesion was attributed to these proteins [56,60], although adhesion mediated by these cytoplasmic chaperones remains controversial.…”

“…Trigger factor, another chaperone with peptidyl-prolyl cis-trans isomerization that assists proteins in its proper folding and maturation [58], was shown to contribute to stress tolerance and alter the expression of genes involved in virulence in S. suis [59] and other pathogenic streptococci [60]. Besides assisting in stress responses, a role in adhesion was attributed to these proteins [56,60], although adhesion mediated by these cytoplasmic chaperones remains controversial. Even when they lack a signal peptide required for secretion and a cell wall anchor motif, they were partially found at the cell surface [60].…”

“…Besides assisting in stress responses, a role in adhesion was attributed to these proteins [56,60], although adhesion mediated by these cytoplasmic chaperones remains controversial. Even when they lack a signal peptide required for secretion and a cell wall anchor motif, they were partially found at the cell surface [60]. Since such adhesion properties were inferred by the attenuated adhesion capacity of mutants compared to wildtype, it could be possible that these chaperones may affect the assembly or the amount of adhesins present at the surface and therefore their role in adhesion is likely indirect.…”