Differential virulence and immune recognition of Klebsiella pneumoniae O-antigen subtypes O2α and O2β

作者：Wantuch PL, Robinson LS, Knoot CJ, Harding CM, Rosen DA · 发表于：Infection and immunity · 年份：2026 · DOI：10.1128/iai.00538-25 · 被引用次数：17 · 研究领域：Klebsiella pneumoniae、O Antigens、Klebsiella Infections、Animals、Virulence、Mice、Virulence Factors、Female、Disease Models, Animal、Immunity, Innate

Klebsiella pneumoniae infections are sharply on the rise among at-risk populations. K. pneumoniae has nine serogroups of O-antigens. Recently, additional O-antigen subtypes within these serogroups have been identified; the contributions of these subtypes to pathogenic fitness and their immunogenicity, functional antibody responses, and cross-reactivity are unknown. We investigated how the addition of the single-branched galactose in O-antigen subtype O2b compared to O2a alters its virulence and host immune responses. We deleted the gmlABC region of an O2b strain of K. pneumoniae, converting it to an otherwise isogenic O2a strain. Complementation of this mutant allowed us to identify the specific genes responsible for the addition of the single branched galactose of O2b. Experiments using the O2a mutant and its parent O2b strain confirmed similar phenotypic expression of virulence factors beyond the O-antigen. Well-established murine models of pneumonia were used to determine the pulmonary fitness of the strains and assess the host innate immune responses. Complement-mediated killing assays suggested differences in susceptibility to innate immune defenses, with the O2a mutant being more susceptible to serum killing. Lastly, using polysaccharide-protein bioconjugate vaccines against these specific O-antigen subtypes, we determined that only partial cross-reactivity and protection are elicited. These studies advance our understanding of the immune response to K. pneumoniae O-ant...