Contribution of lipopolysaccharide to pathogenicity of Haemophilus influenzae: comparative virulence of genetically-related strains in rats

Zwahlen, A; Rubin, Lorry G.; Moxon, E. Richard

doi:10.1016/0882-4010(86)90008-2

Cited by 100 publications

(60 citation statements)

References 29 publications

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“…RM135 appeared highly virulent, producing massive bacteremia on intraperitoneal inoculation that was indistinguishable from that with RM154. Studies with the same strain given intranasally have confirmed its virulence (26). In contrast, similar inocula of RM1071 and RM8055 gave rise to significantly lower bacteremia at 48 h. Nonetheless, at 5 days animals infected with these strains were still bacteremic and also had meningitis; within the CSF there was no apparent restriction on growth of any strain.…”

Section: * Corresponding Authormentioning

confidence: 78%

“…One of these, RM1071, showed a hybridization pattern of EcoRI restriction fragments superficially very similar to that exhibited by spontaneous capsule-deficient mutants of serotype b strains, in which the cap b locus is known to be reduced to a single copy (11,12). The other clinical isolate, RM8055, showed a hybridization pattern of EcoRI restriction fragments indistinguishable from that exhibited by a third strain, RM135, which is a type b laboratory transformant of strain Rd (a capsule-deficient mutant of a serotype d strain) (26).…”

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confidence: 86%

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Capsulation and gene copy number at the cap locus of Haemophilus influenzae type b

Kroll

Moxon

1988

J Bacteriol

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Although more than 98% of natural isolates of Haemophilus influenzae type b carry a duplication of 17 kilobases (kb) of DNA at the chromosomal capsulation locus, only one copy is required for capsulation. In one laboratory-derived and two clinical type b strains, the capsulation locus had a single copy of this 17-kb segment, together with 1.3 kb of DNA identified as lying between the repeats of the duplicated locus. This 1.3 kb appears to be crucial for capsule production, since strains lacking it, although retaining a 17-kb segment, were capsule deficient. On comparing capsule polysaccharide production by these three type b strains with that by a prototypic type b strain with a duplicated locus, a gene dosage effect was demonstrated, with a halving of detectable polysaccharide in the single-copy strains. Despite this reduction in polysaccharide, these strains retained virulence potential as evidenced by bacteremia and meningitis in infant rats. As well as subserving augmented capsule polysaccharide production, a duplicated configuration of the type b cap locus endows strains with genetic instability not found in capsulate single-copy variants. We speculate that a survival advantage might be conferred on strains carrying a duplication at this locus as a result of gene dosage, the genetic instability of the locus, or both.Haemophilus influenzae causes bacterial meningitis and other life-threatening infections in young children and represents a significant health hazard all over the world. Type b strains are responsible for over 95% of invasive infections caused by H. influenzae (25), and the type b capsule, a polymer of ribose and ribitol-5-phosphate (PRP) (8), has been shown to be an important determinant of virulence (14,15).

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Section: * Corresponding Authormentioning

confidence: 78%

mentioning

confidence: 86%

Capsulation and gene copy number at the cap locus of Haemophilus influenzae type b

Kroll

Moxon

1988

J Bacteriol

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“…H. influenzae strain Rd is a longtime laboratory strain and is a spontaneous capsuledeficient mutant of a type d isolate, containing an IS1016 element but no cap gene (12). H. influenzae strain RM135 is a transformant of strain Rd that harbors a single copy of the cap b locus and expresses the type b capsule (47). E. coli DH5␣ has been previously described (15).…”

Section: Methodsmentioning

confidence: 99%

The Haemophilus influenzae Type b hcsA and hcsB Gene Products Facilitate Transport of Capsular Polysaccharide across the Outer Membrane and Are Essential for Virulence

2006

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Haemophilus influenzae type b is a common cause of invasive bacterial disease, especially among children in underdeveloped countries. The type b polysaccharide capsule is a polymer of ribose and ribitol-5-phosphate and is a critical determinant of virulence. Expression of the type b capsule is dependent upon the cap b locus, which consists of three functionally distinct regions, designated regions 1 to 3. Region 3 contains the hcsA and hcsB genes, which share significant homology with genes that have been implicated in encapsulation in other pathogenic bacteria but have unclear functions. In this study, we inactivated hcsA alone, hcsB alone, and both hcsA and hcsB together and examined the effects of these mutations on polysaccharide transport and bacterial virulence properties. Inactivation of hcsA alone resulted in accumulation of polysaccharide in the periplasm and a partial decrease in surface-associated polysaccharide, whereas inactivation of hcsB alone or of both hcsA and hcsB together resulted in accumulation of polysaccharide in the periplasm and complete loss of surfaceassociated polysaccharide. All mutations eliminated serum resistance and abrogated bacteremia and mortality in neonatal rats. These results indicate that the hcsA and hcsB gene products have complementary functions involved in the transport of polysaccharide across the outer membrane and are essential for virulence.

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“…Rd-/b-/02 is a spontaneous, one step, capsuledeficient mutant derived from Rd-/b'/02. Rd-/b-/02 does not make any polyribosyl-ribitol phosphate capsule (by immunofluorescence [15] or ELISA, with a lower limit of dectability of 0.1 ng/ml [161) because it has a mutation in a defined locus within the chromosomal region required for type b capsular expression (17). Additional experiments also utilized another H. influenzae type b (strain Eagan), which has been shown to produce meningitis in experimental animals (especially infant rats) and is the classic strain used in those models.…”

Section: Methodsmentioning

confidence: 99%

Role of cerebrospinal fluid pleocytosis and Haemophilus influenzae type b capsule on blood brain barrier permeability during experimental meningitis in the rat.

Lesse¹,

Moxon²,

Zwahlen³

et al. 1988

J. Clin. Invest.

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Contribution of lipopolysaccharide to pathogenicity of Haemophilus influenzae: comparative virulence of genetically-related strains in rats

Cited by 100 publications

References 29 publications

Capsulation and gene copy number at the cap locus of Haemophilus influenzae type b

Capsulation and gene copy number at the cap locus of Haemophilus influenzae type b

The Haemophilus influenzae Type b hcsA and hcsB Gene Products Facilitate Transport of Capsular Polysaccharide across the Outer Membrane and Are Essential for Virulence

Role of cerebrospinal fluid pleocytosis and Haemophilus influenzae type b capsule on blood brain barrier permeability during experimental meningitis in the rat.

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