Role of Intravascular Replication in the Pathogenesis of Experimental Bacteremia Due to Haemophilus influenzae Type b

Lg, Rubin; Zwahlen, A; Moxon, E. Richard

doi:10.1093/infdis/152.2.307

Cited by 27 publications

(12 citation statements)

References 10 publications

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“…This macrophage-dependent clearance is critical in protecting the host from disseminated infection (8). Virulent H. influenzae type b, which can cause sustained, high-magnitude bacteremia, does so by evading or overwhelming antibody-independent mechanisms of host defense (9)(10)(11)(12). The mechanisms by which this organism evades host defenses, however, are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Role of complement in mouse macrophage binding of Haemophilus influenzae type b.

Noel

Mosser²,

Edelson³

1990

J. Clin. Invest.

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Previous in vivo studies demonstrated that clearance of encapsulated Haemophilus influenzae from blood is associated with the deposition of C3 on these bacteria and is independent of the later complement components (C5-C9). Since clearance of encapsulated bacteria is determined by phagocytosis of bacteria by fixed tissue macrophages, we studied the interaction of H. influenzae type b with macrophages in vitro. Organisms bound to macrophages in the presence of nonimmune serum. Binding was not evident in heat-treated serum or in serum from complement depleted animals and was inhibited by F(ab')2 fragments of antibody to C3 and by blockade of the macrophage complement receptor type 3. The majority of organisms bound in the presence of complement alone remained extracellular.

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Section: Introductionmentioning

confidence: 99%

Role of complement in mouse macrophage binding of Haemophilus influenzae type b.

Noel

Mosser²,

Edelson³

1990

J. Clin. Invest.

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“…For example, Haemophilus influenza and Neisseria meningitidis are commensal bacteria of the upper respiratory tract that can cause life-threatening diseases once they invade their host (11)(12)(13)(14)(15)(16). Upon host entry, H. influenza and N. meningitidis replicate in the blood stream, resulting in a steadily increasing bacteremia within hours after infection (12,(17)(18)(19).…”

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confidence: 99%

Protozoan predation, diversifying selection, and the evolution of antigenic diversity in Salmonella

Wildschutte

Wolfe

Tamewitz

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

147

142

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Extensive population-level genetic variability at the Salmonella rfb locus, which encodes enzymes responsible for synthesis of the O-antigen polysaccharide, is thought to have arisen through frequency-dependent selection (FDS) by means of exposure of this pathogen to host immune systems. The FDS hypothesis works well for pathogens such as Haemophilus influenzae and Neisseria meningitis, which alter the composition of their O-antigens during the course of bloodborne infections. In contrast, Salmonella remains resident in epithelial cells or macrophages during infection and does not have phase variability in its O-antigen. More importantly, Salmonella shows host-serovar specificity, whereby strains bearing certain O-antigens cause disease primarily in specific hosts; this behavior is inconsistent with FDS providing selection for the origin or maintenance of extensive polymorphism at the rfb locus. Alternatively, selective pressure may originate from the host intestinal environment itself, wherein diversifying selection mediated by protozoan predation allows for the continued existence of Salmonella able to avoid consumption by host-specific protozoa. This selective pressure would result in high population-level diversity at the Salmonella rfb locus without phase variation. We show here that intestinal protozoa recognize antigenically diverse Salmonella with different efficiencies and demonstrate that differences solely in the O-antigen are sufficient to allow for prey discrimination. Combined with observations of the differential distributions of both serotypes of bacterial species and their protozoan predators among environments, our data provides a framework for the evolution of high genetic diversity at the rfb locus and host-specific pathogenicity in Salmonella.T he enteric pathogen Salmonella enterica presents at least 70 different O-antigens [the outermost structure of the Gramnegative lipopolysaccharide (LPS)] to mammalian immune systems (1); this polysaccharide decorates the outer surface of the cell. Historically, extensive genetic diversity at the rfb locus, which encodes enzymes directing O-antigen synthesis (2-6), has been attributed to frequency-dependent selection (FDS) (7,8) imposed by the host immune system (5, 9, 10). Novel rfb loci would have an advantage because their cognate O-antigens would be unrecognized by immune systems (Fig. 1A); strains carrying rare loci would have higher fitness and would avoid rapid stochastic loss, rising to higher frequency. Yet selective advantages decrease with abundance; as a result, strains with common rfb loci cannot dominate the population or elicit a selective sweep (7) because their fitnesses become lower as they become more abundant. In concert, FDS prevents the loss of rare alleles or the dominance of common alleles, thus maintaining diversity (8).According to the FDS model, expression of different LPS molecules through gene regulation allows invading bacteria to escape host immunity, survive, and proceed throughout its life cycle; this hypothesis explains...

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“…This may be due to either a different rate of growth (9) or an apparently slower multiplication in animals (because the observed rate is the net result of bacterial multiplication and those host mechanisms that result in bacterial clearance). We have recently provided evidence suggesting that the pathogenesis of experimental Haemophilus influenzae type b bacteremia involves efficient intravascular rpplication (17).…”

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confidence: 99%

Comparison of in vivo and in vitro multiplication rates of Haemophilus influenzae type b

Rubin¹

1986

Infect Immun

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A model of invasive Haemophilus influenzae type b disease in rats was used to compare the net in vivo and in vitro multiplication rates of this bacterium. In both the blood of rats and in vitro cultures (fresh rat blood or enriched broth) there was an exponential increase in the number of CFU per milliliter with calculated net mean generation times as follows: sham-operated rats, 82 ± 39 min (n = 5); asplenic rats, 34 ± 5 min (n = 13); broth, 26 ± 4 min (n = 12); rat blood, 24 + 1 min (n = 14). Thus, in vivo multiplication of H. influenzae type b can be extremely efficient.

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Role of Intravascular Replication in the Pathogenesis of Experimental Bacteremia Due to Haemophilus influenzae Type b

Cited by 27 publications

References 10 publications

Role of complement in mouse macrophage binding of Haemophilus influenzae type b.

Role of complement in mouse macrophage binding of Haemophilus influenzae type b.

Protozoan predation, diversifying selection, and the evolution of antigenic diversity in Salmonella

Comparison of in vivo and in vitro multiplication rates of Haemophilus influenzae type b

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