Conserved and nonconserved epitopes among Haemophilus influenzae type b pili

Gilsdorf, Janet R.; McCrea, Kirk W.; Forney, Larry J.

doi:10.1128/iai.58.7.2252-2257.1990

Cited by 31 publications

(36 citation statements)

References 31 publications

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“…PV rates of a dinucleotide repeat tract were also investigated in strain Eagan by measuring pilus PV, the expression of which is controlled by nine 5′TA repeats. Rates of pilus switching were determined using a polyclonal serum specific for the Eagan pilus (Gilsdorf et al ., 1990). The rate of switching from OFF‐to‐ON was 7.1 × 10 −6 mutations/division for strain Eagan, whereas the rates for the EaganΔ polI kan and EaganΔ polI tet mutants were 2.6‐ and 2.1‐fold higher, respectively.…”

Section: Resultsmentioning

confidence: 99%

Mutations inpollbut notmutSLHdestabilizeHaemophilus influenzaetetranucleotide repeats

2002

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Haemophilus influenzae (Hi), an obligate upper respiratory tract commensal/pathogen, uses phase variation (PV) to adapt to host environment changes. Switching occurs by slippage of nucleotide repeats (microsatellites) within genes coding for virulence molecules. Most such microsatellites in Hi are tetranucleotide repeats, but an exception is the dinucleotide repeats in the pilin locus. To investigate the effects on PV rates of mutations in genes for mismatch repair (MMR), insertion/deletion mutations of mutS, mutL, mutH, dam, polI, uvrD, mfd and recA were constructed in Hi strain Rd. Only inactivation of polI destabilized tetranucleotide (5'AGTC) repeat tracts of chromosomally located reporter constructs, whereas inactivation of mutS, but not polI, destabilized dinucleotide (5'AT) repeats. Deletions of repeats were predominant in polI mutants, which we propose are due to end-joining occurring without DNA polymerization during polI-deficient Okazaki fragment processing. The high prevalence of tetranucleotides mediating PV is an exceptional feature of the Hi genome. The refractoriness to MMR of hypermutation in Hi tetranucleotides facilitates adaptive switching without the deleterious increase in global mutation rates that accompanies a mutator genotype.

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Section: Resultsmentioning

confidence: 99%

Mutations inpollbut notmutSLHdestabilizeHaemophilus influenzaetetranucleotide repeats

2002

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“…Native H. influenzae pili demonstrate a high degree of immunologic heterogeneity with both polyclonal antisera and monoclonal antibodies (Brinton et al ., 1989; Gilsdorf et al. , 1990; 1992; Palmer and Munson, 1992).…”

Section: Discussionmentioning

confidence: 99%

Evidence for donor strand complementation in the biogenesis of Haemophilus influenzae haemagglutinating pili

Krasan

Sauer²,

Cutter

et al. 2000

Molecular Microbiology

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SummaryHaemophilus influenzae haemagglutinating pili are surface appendages that promote attachment to host cells and facilitate respiratory tract colonization, an essential step in the pathogenesis of disease. In contrast to other well-characterized forms of pili, H. influenzae haemagglutinating pili are two-stranded helical structures. Nevertheless, haemagglutinating pili are assembled by a pathway that involves a periplasmic chaperone and an outer membrane usher, analogous to the prototype pathway involved in the biogenesis of Escherichia coli P pili. In this study, we performed site-directed mutagenesis of the H. influenzae HifB chaperone and HifA major pilus subunit at positions homologous to sites important for chaperone±sub-unit interactions and subunit oligomerization in P pili. Mutations at putative subunit binding pocket residues in HifB or at the penultimate tyrosine in HifA abolished formation of HifB±HifA periplasmic complexes, whereas mutations at the 214 glycine in HifA had no effect on HifB±HifA interactions but abrogated HifA oligomerization. To define further the constraints of the interaction between HifA and HifB, we examined the interchangeability of pilus gene cluster components from H. influenzae type b strain Eagan (hifA-hifE Eag ) and the related H. influenzae biogroup aegyptius strain F3031 (hifA-hifE F3031 ). Functional pili were assembled both with HifA Eag and the strain F3031 gene cluster and with HifA F3031 and the strain Eagan gene cluster, underscoring the flexibility of the H. influenzae chaperone/usher pathway in incorporating HifA subunits with significant sequence diversity. To gain additional insight into the interactive surfaces of HifA and HifB, we aligned HifA sequences from 20 different strains and then modelled the HifA structure based on the recently crystallized PapD± PapK complex. Analysis of the resulting structure revealed high levels of sequence conservation in regions predicted to interact with HifB, and maximal sequence diversity in regions potentially exposed on the surface of assembled pili. These results suggest broad applicability of structure±function relationships identified in studies of P pili, including the concepts of donor strand complementation and donor strand exchange. In addition, they provide insight into the structure of HifA and suggest a basis for antigenic variation in H. influenzae haemagglutinating pili.

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“…In contrast, pili from non-typable strains are more diverse [78]. Although the major structural subunits from di¡erent strains show substantial similarity in amino acid sequence, antiserum raised against a particular piliated strain is usually not broadly reactive, indicating that immunodominant epitopes in the mature pilus structure are likely conformational and strain-speci¢c in nature [77,79]. As an example, in the chinchilla model of otitis media, Karasic et al found that immunization with puri¢ed pili protected animals from challenge with the homologous piliated strain, but failed to protect from challenge with a heterologous piliated strain [80].…”

Section: Hemagglutinating Pilimentioning

confidence: 99%

“…This observation implies that the repeats exist purely for the purpose of phase variation. The switching on and o¡ of these biosynthetic genes results in alterations in reactivity with monoclonal antibodies directed against speci¢c oligosaccharide epitopes [1771 79,181], suggesting that LOS phase variation may facilitate evasion of the antibody response to natural infection.…”

Section: Los Variationmentioning

confidence: 99%

Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae

Rao¹

1999

FEMS Microbiology Reviews

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Non-typable Haemophilus influenzae is a common commensal organism in the human upper respiratory tract and an important cause of localized respiratory tract disease. The pathogenesis of disease begins with bacterial colonization of the nasopharynx, a process that involves establishment on the mucosal surface and evasion of local immune mechanisms. Under the proper circumstances, the organism spreads contiguously to the middle ear, the sinuses, or the lungs, and then stimulates a brisk inflammatory response, producing symptomatic infection. In this review, we summarize our present understanding of the molecular determinants of this sequence of events. Continued investigation of the molecular mechanism of non-typable H. influenzae pathogenicity should facilitate development of novel approaches to the treatment and prevention of H. influenzae disease.

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Conserved and nonconserved epitopes among Haemophilus influenzae type b pili

Cited by 31 publications

References 31 publications

Mutations inpollbut notmutSLHdestabilizeHaemophilus influenzaetetranucleotide repeats

Mutations inpollbut notmutSLHdestabilizeHaemophilus influenzaetetranucleotide repeats

Evidence for donor strand complementation in the biogenesis of Haemophilus influenzae haemagglutinating pili

Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae

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