O-antigen polysaccharides in Klebsiella pneumoniae: structures and molecular basis for antigenic diversity

SUMMARYKlebsiella pneumoniae is a gram-negative species, whose isolates are found in the environment and as commensals in the human gastrointestinal tract. This bacterium is among the leading causes of a range of nosocomial and community-acquired infections, particularly in immunocompromised individuals, where it can give rise to pneumonia, urinary tract infections, septicemia, and liver abscesses. Treatment of K. pneumoniae infections is compromised by the emergence of isolates producing carbapenemase and extended-spectrum β-lactamase enzymes, making it a high priority for new therapeutic approaches including vaccination and immunoprophylaxis. One potential target for these strategies is the O-antigen polysaccharide component of lipopolysaccharides, which are important virulence determinants for K. pneumoniae. Consideration of immunotherapeutic opportunities requires a comprehensive and fundamental understanding of O-polysaccharide structures, distribution of particular O serotypes in clinical isolates, and the potential for antigenic diversification. The number of recognized K. pneumoniae O-polysaccharide antigens has varied over time, complicated by the observation that some examples share similar structural (and potentially antigenically cross-reactive) elements, and by the existence of genetic loci for which corresponding O-polysaccharide structures have yet to be determined. Here, we provide a comprehensive integration of the current carbohydrate structures and genetic information, together with a proposal for an updated classification system for K. pneumoniae O-antigens, that is being implemented in Kaptive for molecular serotyping. The accumulated insight into O-polysaccharide assembly pathways is used to describe the molecular basis for O-antigen diversity in K. pneumoniae.