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

-glucosamine (PNAG) surface capsule is synthesized byfour proteins encoded in genetic loci designated intercellular ad-hesion in Staphylococcus aureus or polyglucosamine in selectedGram-negative bacterial pathogens. We report that many micro-bial pathogens lacking an identifiable intercellular adhesion orpolyglucosamine locus produce PNAG, including Gram-positive,Gram-negative, and fungal pathogens, as well as protozoa, e.g.,Trichomonas vaginalis, Plasmodium berghei, and sporozoites andblood-stage forms of Plasmodium falciparum. Natural antibody toPNAG is common in humans and animals and binds primarily tothe highly acetylated glycoform of PNAG but is not protectiveagainst infection due to lack of deposition of complement opso-nins. Polyclonal animal antibody raised to deacetylated glycoformsof PNAG and a fully human IgG1 monoclonal antibody that bothbind to native and deacetylated glycoforms of PNAG mediatedcomplement-dependent opsonic or bactericidal killing and pro-tected mice against local and/or systemic infections by Streptococ-cuspyogenes,Streptococcuspneumoniae,Listeriamonocytogenes,Neisseria meningitidis serogroupB, Candida albicans,andP. bergheiANKA, and against colonic pathology ina modelofinfectious colitis.PNAG is also a capsular polysaccharide for Neisseria gonorrhoeaeand nontypable Hemophilus influenzae, and protects cells from en-vironmental stress. Vaccination targeting PNAG could contribute toimmunity against serious and diverse prokaryotic and eukaryoticpathogens, and the conserved production of PNAG suggests that itis a critical factor in microbial biology.