Surface antigen exposure by bismuth dimercaprol suppression of Klebsiella pneumoniae capsular polysaccharide

The bacterial capsule is an important virulence determinant in animal and p lant disease, Bacterial capsule and slime can be inhibited by bismuth compo unds, especially when complexed with lipophilic thiol chelators, Bismuth di mercaprol (BisBAL) at 1 ppm of Bi3+ repressed Klebsiella pneumoniae capsule expression in defined medium by nearly 90%, which exposed subsurface struc tures. The phagocytic index for BisBAL-treated bacteria increased from <10 to 360 bacteria per 100 neutrophils in the presence of complement and antic apsular or anti-O antigen antiserum. BisBAL treatment also enhanced the rea ctivity of monoclonal antibodies (MAbs) specific for the O1-antigen lipopol ysaccharide (LPS) or the LPS core in a dose-dependent manner as indicated b y the results of enzyme-linked immunosorbent assays. When anti-Ol MAb was u sed, the reactivity increased significantly for fully encapsulated O1:K1 or O1:K2 cells but not for O1:K- cells. Deposition of C3b also increased sign ificantly for BisBAL-treated O1:K1 or O1:K2 cells but not for O1:K- cells. Survival of a serum-sensitive strain was <0.1% when nonimmune human serum a bsorbed with O1:K1 cells was used and 107% when BisBAL-treated cells were u sed for absorption. Outer membrane proteins were also more accessible on th e surface of K. pneumoniae after BisBAL treatment. Thus, at subinhibitory l evels, BisBAL inhibited capsule expression, which promoted phagocytosis, en hanced the reactivity of specific antibodies for LPS O antigen, LPS core ep itopes, or outer-membrane proteins, and enhanced complement interaction wit h encapsulated K. pneumoniae, By unmasking bacterial surface structures and enhancing the immune system reactivity to bacteria, bismuth thiols may pro ve useful as adjuncts for vaccination.