Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens

Abstract

Microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. A β-(1→6)-linked poly-N-acetyl-D-glucosamine (PNAG) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in Staphylococcus aureus or polyglucosamine in selected Gram-negative bacterial pathogens. We report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce PNAG, including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e.g., Trichomonas vaginalis, Plasmodium berghei, and sporozoites and blood-stage forms of Plasmodium falciparum. Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins. Polyclonal animal antibody raised to deacetylated glycoforms of PNAG and a fully human IgG1 monoclonal antibody that both bind to native and deacetylated glycoforms of PNAG mediated complement-dependent opsonic or bactericidal killing and protected mice against local and/or systemic infections by Streptococcus pyogenes, Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis serogroup B, Candida albicans, and P. berghei ANKA, and against colonic pathology in a model of infectious colitis. PNAG is also a capsular polysaccharide for Neisseria gonorrhoeae and nontypable Hemophilus influenzae, and protects cells from environmental stress. Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology.immunotherapy | infectious diseases | malaria | carbohydrates | animal models

Pathogen-mediated manipulation of arthropod microbiota to promote infection

“…To elucidate the importance of IAFGP in shaping the tick gut microbiota, we injected the antibiofilm peptide, P1, derived from IAFGP (25), and showed that this improved A. phagocytophilum infection, in ticks. Exopolysaccharides such as PNAG, a major component of bacterial biofilms, are broadly distributed among diverse microbes (27). Using antibodies directed against PNAG as a proxy to gauge biofilms within the tick, P1-injected I. scapularis guts showed a marked reduction of biofilms, similar those with A. phagocytophilum infection.…”

“…PNAG is broadly distributed in diverse microbes and can be detected by a specific antibody (27). Having observed native biofilm formation in tick guts using a PNAG antibody (SI Appendix, Fig.…”

Structural Basis for the De-N-acetylation of Poly-β-1,6-N-acetyl-d-glucosamine in Gram-positive Bacteria

“…The conserved exopolysaccharide known as polysaccharide intercellular adhesin was originally identified in the biofilms of S. epidermidis (11) and Staphylococcus aureus (12) and has now been shown to be produced by various Gram-negative bacteria (13)(14)(15)(16)(17)(18)(19) and higher eukaryotes (20). Polysaccharide intercellular adhesin is synthesized as a ␤-1,6-linked poly-N-acetyl-Dglucosamine (PNAG) 5 polymer and subsequently modified by partially de-N-acetylation and/or O-succinylation.…”

Active and Passive Immunization Against Staphylococcus aureus Periprosthetic Osteomyelitis in Rats

“…The greater effect of the post-infection goat antiserum on the ica − strain compared to the ica + strain suggests that the presence of the PNAG antigen on the bacterial surface reduces the efficacy of the antibodies against the non-PNAG antigens on the bacterial surface. PNAG, also known as intercellular adhesion polysaccharide (20), is a surface polymer produced by both S. aureus and S. epidermis, and many other pathogens (21). PNAG promotes biofilm formation and enhances staphylococcal virulence in mouse infection models (12,22).…”