Characterization of a mutant of Haemophilus influenzae type b lacking the P2 major outer membrane protein

Cope, Leslie D.; Pelzel, Sharon E.; Latimer, Jo L.; Hansen, Eric J.

doi:10.1128/iai.58.10.3312-3318.1990

Cited by 28 publications

(12 citation statements)

References 57 publications

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“…Modulation of the Band T-cell response in rats has been shown to influence the ability of P2 to protect them from challenge with a homologous NTHi strain (110). The interstrain heterogeneity (143) and antigenic drift (74,75) of the organism and its ability to survive in the absence of P2 (17,27,171) may preclude the use of P2 as a vaccine candidate except as a carrier of other proteins inserted into its hypervariable regions (136a).…”

Section: Outer Membrane Proteinsmentioning

confidence: 99%

NontypeableHaemophilus influenzae: Pathogenesis and Prevention

Foxwell

Kyd

Cripps

1998

Microbiol Mol Biol Rev

204

107

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SUMMARY In this paper, we describe the ability of nontypeable Haemophilus influenzae (NTHi) to coexist with the human host and the devastating results associated with disruption of the delicate state of balanced pathogenesis, resulting in both acute and chronic respiratory tract infections. It has been seen that the strains of NTHi causing disease show a marked genetic and phenotypic diversity but that changes in the lipooligosaccharide (LOS) and protein size and antigenicity in chronically infected individuals indicate that individual strains of NTHi can remain and adapt themselves to avoid expulsion from their infective niche. The lack of reliance of NTHi on a single mechanism of attachment and its ability to interact with the host with rapid responses to its environment confirmed the success of this organism as both a colonizer and a pathogen. In vitro experiments on cell and organ cultures, combined with otitis media and pulmonary models in chinchillas, rats, and mice, have allowed investigations into individual interactions between NTHi and the mammalian host. The host-organism interaction appears to be a two-way process, with NTHi using cell surface structures to directly interact with the mammalian host and using secreted proteins and LOS to change the mammalian host in order to pave the way for colonization and invasion. Many experiments have also noted that immune system evasion through antigenic variation, secretion of enzymes and epithelial cell invasion allowed NTHi to survive for longer periods despite a specific immune response being mounted to infection. Several outer membrane proteins and LOS derivatives are discussed in relation to their efficacy in preventing pulmonary infections and otitis media in animals. General host responses with respect to age, genetic makeup, and vaccine delivery routes are considered, and a mucosal vaccine strategy is suggested.

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Section: Outer Membrane Proteinsmentioning

confidence: 99%

NontypeableHaemophilus influenzae: Pathogenesis and Prevention

Foxwell

Kyd

Cripps

1998

Microbiol Mol Biol Rev

204

107

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“…Southern analysis of Hib and nontypeable H. infiuenzae strains. This blot contains SnaBI-digested genomic DNA from a variety of H. influenzae strains described previously (8,11,14,32). The DNA probe was derived from the intragenic region of hifC.…”

Section: Discussionmentioning

confidence: 99%

“…E. coli HB101 and DH5a were used as hosts for construction of specific insertional mutations and for amplification of plasmid DNA for nucleotide sequence analysis. The Hib and nontypeable H. influenzae strains used in the Southern analysis have been described previously (8,11,14,32).…”

Section: Methodsmentioning

confidence: 99%

Identification of a gene essential for piliation in Haemophilus influenzae type b with homology to the pilus assembly platform genes of gram-negative bacteria

et al. 1994

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Haemophilus influenzae type b (Hib) pili are complex filamentous surface structures consisting predominantly of pilin protein subunits. The gene encoding the major pilin protein subunit of Hib adherence pili has been cloned and its nucleotide sequence has been determined. In order to identify specific accessory genes involved in pilus expression and assembly, we constructed isogenic Hib mutants containing insertional chromosomal mutations in the DNA flanking the pilin structural gene. These mutants were screened for pilin production, pilus expression, and hemagglutination. Pili and pilin production were assessed by immunoassays with polyclonal antisera specific for pilin and pili of Hib strain Eagan. Hemagglutination was semiquantitatively evaluated in a microtiter plate assay. Six Hib mutants produced proteins immunoreactive with antipilin antiserum but no longer produced structures reactive with antipilus antiserum. In addition, the mutants were unable to agglutinate human erythrocytes. Nucleotide sequence analysis localized the insertion sites in the six mutants to a 2.5-kb open reading frame upstream of the pilin structural gene and immediately downstream of an Hib pilin chaperone gene. The amino acid sequence encoded by this open reading frame has significant homology to members of the pilus assembly platform protein family, including FhaA of Bordetella pertussis, MrkC of Klebsiella pneumoniae, and the Escherichia coli assembly platform proteins FimD and PapC. This open reading frame, designated hifC, appears to represent a gene essential to Hib pilus biogenesis that has genetic and functional similarity to the pilus platform assembly genes of other gram-negative rods.

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“…Hib strain M42 and its piliated phase variant, M43p+, and Ela (Eagan) and its piliated phase variant, Elap+, have been described previously (21,27). Hib strain DL42 has been described previously (4). Its piliated phase variant, DL42p+, was obtained by hemagglutination selection (21).…”

Section: Methodsmentioning

confidence: 99%

Paradoxical effect of pilus expression on binding of antibodies by Haemophilus influenzae

et al. 1993

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Haemophilus influenzae type b (Hib) pili are surface proteins that are associated with the ability of Hib to attach to human epithelial cells. Like pilus expression of other bacteria, expression of Hib pili undergoes phase variation. We observed that Hib in the piliated phase (Hib p+) bound monoclonal antibodies directed against six conserved, surface-exposed, nonpilus Hib outer membrane epitopes to a greater extent than Hib in the nonpiliated phase (Hib p-). However, after extended incubation, p+ and pcells bound these antibodies in a similar fashion. The differential in nonpilus antibody binding to p+ and p-Hib was not related to the presence of the type b capsule. In addition, Hib p+ organisms whose pilin gene was insertionally inactivated and did not produce pili and Hib in the nonpiliated phase bound the nonpilus Hib antibodies similarly. Hib p+ and porganisms did not differ in their binding of anti-type b capsule antibody, and the binding was specific for the epitopes recognized by the antibodies. In complement-dependent bactericidal assays, the nonpilus antibodies killed Hib p+ more effectively than Hib p-. The increased binding to, and killing of, Hib p+ by a variety of nonpilus antibodies may be important for host defense against invasive Hib.

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Characterization of a mutant of Haemophilus influenzae type b lacking the P2 major outer membrane protein

Cited by 28 publications

References 57 publications

NontypeableHaemophilus influenzae: Pathogenesis and Prevention

NontypeableHaemophilus influenzae: Pathogenesis and Prevention

Identification of a gene essential for piliation in Haemophilus influenzae type b with homology to the pilus assembly platform genes of gram-negative bacteria

Paradoxical effect of pilus expression on binding of antibodies by Haemophilus influenzae

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