The mammalian intestine harbors a beneficial microbiota numbering approximately 10(12) organisms per gram of colonic content. The host tolerates this tremendous bacterial load while maintaining the ability to efficiently respond to pathogenic organisms. In this study, we show that the Bacteroides use a mammalian-like pathway to decorate numerous surface capsular polysaccharides and glycoproteins with l-fucose, an abundant surface molecule of intestinal epithelial cells, resulting in the coordinated expression of this surface molecule by host and symbiont. A Bacteroides mutant deficient in the ability to cover its surface with L-fucose is defective in colonizing the mammalian intestine under competitive conditions.

Herein we report studies with a novel combination vaccine that, when administered to mice, conferred protection against highly virulent strains of Francisella tularensis by stimulating both arms of the immune system. Our earlier studies with Ft.LVS::wbtA, an O-polysaccharide (OPS)-negative mutant derived from the available live vaccine strain of F. tularensis (Ft.LVS), elucidated the role of antibodies to the OPS-a key virulence determinant-in protection against virulent type A organisms. However, when expressed on the organism, the OPS enhances virulence. In contrast, in purified form, the OPS is completely benign. We hypothesized that a novel combination vaccine containing both a component that induces humoral immunity and a component that induces cellular immunity to this intracellular microbe would have an enhanced protective capacity over either component alone and would be much safer than the LVS vaccine. Thus we developed a combination vaccine containing both OPS (supplied in an OPS-tetanus toxoid glycoconjugate) to induce a humoral antibody response and strain Ft.LVS::wbtA (which is markedly attenuated by its lack of OPS) to induce a cell-mediated protective response. This vaccine protected mice against otherwise-lethal intranasal and intradermal challenge with wildtype F. tularensis strains Schu S4 (type A) and FSC 108 (type B). These results represent a significant advance in our understanding of immunity to F. tularensis and provide important insight into the development of a safer vaccine effective against infections caused by clinical type A and B strains of F. tularensis.

One hundred three clinical isolates of Bacteroides fragilis were identified during a two-year period. Most of these isolates were strains of B. fragilis subspecies fragilis, which constitutes a minor component of the fecal flora in comparison with the other subspecies of B. fragilis. By use of several techniques for demonstration of capsules, it was found that only B. fragilis strains classified as subspecies fragilis were encapsulated. An indirect immunofluorescence assay was developed for identification of clinical isolates possessing capsular material that was immunologically similar to that found in the reference strain of B. fragilis subspecies fragilis. All strains examined that were classified as subspecies fragilis were positive in this assay for the capsular material, whereas strains of the other subspecies were negative. This tests represents a rapid and sensitive means of identifying the most prevalent anaerobic gram-negative bacillus involved in human infections. The capsular polysaccharide of B. fragilis subspecies fragilis is a unique factor associated with the predominant subspecies of B. fragilis isolated from clinical material.