Gardnerella Vaginolysin Potentiates Glycan Molecular Mimicry by Neisseria gonorrhoeae

• Published in: The Journal of infectious diseases 2023-12, Vol.228 (11), p.1610-1620
• Main Authors: Morrill, Sydney R, Saha, Sudeshna, Varki, Ajit P, Lewis, Warren G, Ram, Sanjay, Lewis, Amanda L
• Format: Article
• Language: English
• Subjects: Bacteria; Bacterial Proteins - genetics; Complement Factor H; Cytolysins; Editor's Choice; Female; Flow cytometry; Gardnerella - metabolism; Gonorrhea; Gonorrhea - microbiology; HeLa Cells; Humans; Immunity; Intracellular; Lipooligosaccharides; Major; Microbiomes; Mimicry; Molecular Mimicry; N-Acetylneuraminic Acid - metabolism; Neisseria gonorrhoeae; Polysaccharides; Vaginosis; Vaginosis, Bacterial - microbiology; Virulence
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiad391

Abstract Bacterial vaginosis (BV) is a dysbiotic condition of the vaginal microbiome associated with higher risk of infection by Neisseria gonorrhoeae—the cause of gonorrhea. Here we test if one known facet of BV—the presence of bacterial cytolysins—leads to mobilization of intracellular contents that enhance gonococcal virulence. We cloned and expressed recombinant vaginolysin (VLY), a cytolysin produced by the BV-associated bacterium Gardnerella, verifying that it liberates contents of cervical epithelial (HeLa) cells, while vector control preparations did not. We tested if VLY mediates a well-known gonococcal virulence mechanism—the molecular mimicry of host glycans. To evade host immunity, N. gonorrhoeae caps its lipooligosaccharide (LOS) with α2-3-linked sialic acid. For this, gonococci must scavenge a metabolite made inside host cells. Flow cytometry-based lectin-binding assays showed that gonococci exposed to vaginolysin-liberated contents of HeLa cells displayed greater sialic acid capping of their LOS. This higher level of bacterial sialylation was accompanied by increased binding of the complement regulatory protein factor H, and greater resistance to complement attack. Together these results suggest that cytolytic activities present during BV may enhance the ability of N. gonorrhoeae to capture intracellular metabolites and evade host immunity via glycan molecular mimicry. Gonococci can capture intracellular metabolites and use them to mimic host glycans. Here we show that cytolysins present during bacterial vaginosis can enhance this gonococcal virulence mechanism by freeing cervical epithelial intracellular contents.