The molecular basis of pathogenicity in Haemophilus influenzae: comparative virulence of genetically-related capsular transformants and correlation with changes at the capsulation locus cap

Capsulation in distantly related strains of Haemophilus influenzae type b: genetic drift and gene transfer at the capsulation locus

“…RM132 is a mutant of the division I type b strain RM135 (14), which is capsule deficient as the result of a point mutation close to the EcoRV site in the 4.4-kb EcoRI segment. The mutation is located in DNA with type a and b serotype specificity, in a gene tentatively associated with the incorporation of ribitol into the capsule polysaccharide (10,27). Transformation with pJSK32 yielded type b capsulate progeny like RM5684, in which the 4.4-kb EcoRI fragment had been replaced by a 5.5-kb piece (Fig.…”

Invasive Serotype a Haemophilus influenzaeInfections With a Virulence Genotype Resembling Haemophilus influenzae Type b: Emerging Pathogen in the Vaccine Era?

“…Increased capsule may limit opsonophagocytic killing, but in serotype b strains, noncapsular factors also are critical. 18 It is possible that the IS1016-bexA deletion may be linked to other genes that are important in colonization, invasion or other virulence genes. Additional dissection of the virulence mechanisms of invasive Haemophilus is needed.…”

Challenge of Investigating Biologically Relevant Functions of Virulence Factors in Bacterial Pathogens

“…Clear distinctions might need to be made between the scienti¢c merit of using bacteria as probes for investigating cellular functions, such as endocytosis or Table 1. Usefulness of infant rats as a model for investigating the pathogenesis of H. in£uenzae bacteraemia and meningitis bacteria reach the central nervous system by the haematogenous route, not via the cribrifrom plate, following intranasal challenge (Ostrow et al 1979) the probability of meningitis is directly related to the concentration of bacteria in the blood and to their exceeding a critical threshold of greater than 10 3 organisms ml À1 blood (Moxon & Ostrow 1977) the population of organisms recovered from the blood or CSF in the acute phase of bacteraemia and meningitis is the progeny of a few founder bacteria, often a single clone (Moxon & Murphy 1978) opsonophagocytosis, not bactericidal killing, is the major mechanism of in vivo clearance (Weller et al 1978) organisms grown in vivo are relatively resistant to antibody-dependent, complement-mediated killing (in vitro), when compared with organisms grown in vitro (Shaw et al 1976) expression of phosphorylcholine, a phase-variable component of LPS, facilitates nasopharyngeal colonization, whereas its absence increases intravascular survival (Weiser & Pan 1998) expression of type b capsule, per se, confers heightened virulence compared with other capsular polysaccharides (Zwahlen et al 1989) mutations of LPS can attenuate systemic infection even when the bacteria are fully encapsulated (Zwahlen et al 1986) mean generation time of organisms is not less than 50 min in the acute phase of infection (Moxon 1992) the blood is a major site of replication of organisms in the pathogenesis of bacteraemia prior nasopharyngeal infection, or induction of in£ammation, increases susceptibility to bacteraemia following intranasal challenge (Myerowitz 1981) decreased concentrations of glucose in CSF during acute meningitis do not result from increased consumption by organisms or in£ammatory cells seeding the peritoneal cavity of splenectomized rats with fragments of spleen enhances protection against lethal challenge (Moxon & Schwartz 1980) serum antibodies to type b capsular polysaccharide facilitate clearance of organisms from the nasopharynx (Moxon & Anderson 1979) tra¤cking, and the pragmatic issue of their relevance to pathogenesis. For example, the pathogenicity of enteropathogenic Escherichia coli is associated with the e¡ace-ment of microvilli and cytoskeletal rearrangements.…”