FRANCISELLA-TULARENSIS RESISTANCE TO BACTERICIDAL ACTION OF NORMAL HUMAN SERUM

Lipopolysaccharide and outer membranes from the three virulent encapsu lated (Cap(+)) strains of three subspecies of Francisella tularensis a nd their isogenic avirulent capsule-deficient (Cap(-)) mutants were is olated. It was shown that the Cap(-) cells and their outer membranes a lmost completely consumed the available complement of normal human ser um whereas Cap(-) LPS (R-LPS), Cap(+) cells and their components activ ated the complement less effectively. Absorption of normal human serum with Cap(-) strain dramatically reduced the complement consumption fo r homologous strain and its surface structures. This reduction reflect ed the loss of bactericidal antibodies. Addition of antibodies to whol e cells of F. tularensis completely restored complement activity. The cross-absorbing experiments demonstrated that Cap(-) cells more effect ively deplete bactericidal antibodies than homologous virulent strain. From these results it can be concluded that normal human serum is bac tericidal for serum-sensitive Cap(-) F. tularensis strains through the action of complement initiated by the classical complement pathway an d serum resistance of virulent strains is not due to absence of target s for bactericidal antibodies, but is due to their low accessibility b ecause of O-side chains of lipopolysaccharide.