Molecular analysis of two group B streptococcal virulence factors.
Molecular biology has provided new technology for evaluating the traits of bacterial pathogens that are important in the pathogenesis of infections. The ability to derive isogenic strains that differ by a single trait provides a powerful tool for investigating the interaction of a putative virulence factor with the host at any of the various steps in pathogenesis. Recombinant DNA techniques afford the opportunity to clone the genes involved in the biosynthesis of a particular virulence factor. Once the gene(s) are cloned, a vast amount of information can be learned about their composition, structure, and regulation, and similarity with genes in other organisms. Understanding the molecular biology of a virulence factor also provides information about potential targets for future therapies and preventive modalities. The molecular analysis of two virulence factors from the type III group B streptococcus has been reviewed to provide specific examples of how these techniques can be used. The data has shown that the capsular polysaccharide is an essential factor in GBS virulence. The structural influence of sialic acid on the capsule plays a major role in its virulence properties. The importance of the capsule has been tested in several assays to identify its role in pathogenesis. Its primary role appears to be evading host phagocytic mechanisms, but it does not appear to be essential in the vascular response observed during GBS sepsis. Using the isogenic strains, we have also learned that the capsule does not mask a fibronectin receptor on GBS. In contrast to the capsule, the beta-hemolysin of GBS does not appear to be essential for systemic disease once the organism has invaded. Its role in the initial invasive steps in GBS pathogenesis has not been tested, but the availability of isogenic mutants in beta-hemolysin production will allow this question to be answered once the model systems are available.(ABSTRACT TRUNCATED AT 250 WORDS)
Rubens
C E
CE
Department of Pediatrics, University of Washington, Children's Hospital and Medical Center, Seattle 98105.
Wessels
M R
MR
Kuypers
J M
JM
Kasper
D L
DL
Weiser
J N
JN
D000595:Amino Acid Sequence; D000818:Animals; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002999:Clone Cells; D004251:DNA Transposable Elements; D006460:Hemolysin Proteins / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D019158:N-Acetylneuraminic Acid; D011135:Polysaccharides, Bacterial / Q000032:analysis / Q000235:genetics / Q000502:physiology; D051381:Rats; D012794:Sialic Acids / Q000494:pharmacology; D013292:Streptococcus agalactiae / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence
D004251:DNA Transposable Elements; D006460:Hemolysin Proteins; D011135:Polysaccharides, Bacterial; D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid