Structural elucidation and serological studies of emerging Klebsiella pneumoniae capsular polysaccharides K102 and K112

Klebsiella pneumoniae (Kp) is a gram-negative bacterium and a leading cause of several severe infections, including neonatal sepsis in low- and middle-income countries (LMICs). Kp strains display surface carbohydrates, capsular polysaccharides (CPS) and O-antigens, and are classified by capsule serotyping of the CPS into K-antigens. KL102 and KL112 CPS loci have been identified in two Kp high-risk clones, including those associated with neonatal sepsis, being therefore interesting potential targets for vaccine development. Sugar analysis and one- and two-dimensional 1H and 13C NMR spectroscopy studies elucidated the repeating unit structures of the K102(KL102) and K112 (KL112) K-antigens. Interestingly, KL102 is strongly associated with strains of the Kp Sequence Type (ST) 307 high-risk clone. Also KL112 was a K-locus which is prominently associated to the major clade of the Kp ST15 high-risk clone. K102 and K112 glycoconjugates were generated and corresponding hyperimmune sera from rabbits showed some levels of cross-binding (by flow cytometry) and cross-functionality (by serum bactericidal activity) against a panel of heterologous K-types isolated from LMICs. In conclusion, the structures of two new CPS frequently associated with two Kp high-risk clones were elucidated and the potential for simplification of vaccine design through cross-reactivity investigated.