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

Watson, Wendy; Gilsdorf, Janet R.; Tucci, Michelle; McCrea, Kirk W.; Forney, Larry J.; Marrs, Carl F.

doi:10.1128/iai.62.2.468-475.1994

Cited by 33 publications

(31 citation statements)

References 36 publications

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“…The HMWB proteins also show significant low-level similarity to a series of outer membrane ushers involved in pilus biogenesis. Examples include the H. influenzae HifC protein (Watson et al, 1994), the Salmonella enteritidis SefC protein (Clouthier et al, 1993) and the E. coli CS6 usher (CssD). Based on work with PapC, the prototype usher required for the assembly of E. coli P pili, ushers are believed to form outer membrane assembly sites that facilitate dissociation of chaperone-subunit complexes and promote ordered incorporation of subunits into growing pilus rods (Dodson et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Secretion of the Haemophilus influenzae HMW1 and HMW2 adhesins involves a periplasmic intermediate and requires the HMWB and HMWC proteins

Geme

Grass

1998

Molecular Microbiology

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Non-typable Haemophilus influenzae is a common cause of human disease and initiates infection by colonizing the upper respiratory tract. The non-typeable H. influenzae HMW1 and HMW2 non-pilus adhesins mediate attachment to human epithelial cells, an essential step during colonization. In order to facilitate interaction with host cells, HMW1 and HMW2 are localized on the surface of the organism in a process that involves cleavage of a 441-amino-acid N-terminal fragment. In the present study, we investigated the pathway for the secretion of HMW1 and HMW2. Cell fractionation experiments and cryoimmunoelectron microscopy demonstrated that a periplasmic intermediate occurs, suggesting involvement of the Sec machinery. Additional analysis revealed that, ultimately, the proteins are partially released from the surface of the organism. Studies with Escherichia coli harbouring plasmid subclones extended earlier findings and suggested that the secretion of HMW1 requires accessory proteins designated HMW1B and HMW1C, while the secretion of HMW2 requires proteins called HMW2B and HMW2C. Further analysis established that HMW1B/HMW1C and HMW2B/HMW2C are interchangeable, an observation consistent with the high degree of homology between HMW1B and HMW2B and between HMW1C and HMW2C. Additional studies of the hmw1 locus indicated that HMW1B is located in the outer membrane and serves to translocate HMW1 across the outer membrane. In the absence of HMW1B, HMW1 remains unprocessed and is degraded in the periplasmic space, at least in part by the DegP protease. Mutagenesis of an HMW1 N-terminal motif shared with other secreted proteins resulted in diminished processing and extracellular release, suggesting interaction of this motif with the HMW1B protein. Continued investigation of the HMW1 and HMW2 adhesins may provide general insights into protein secretion and bacterial pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Secretion of the Haemophilus influenzae HMW1 and HMW2 adhesins involves a periplasmic intermediate and requires the HMWB and HMWC proteins

Geme

Grass

1998

Molecular Microbiology

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“…Like ShlB, HpmB, HhdB, HxuB, and FhaC, HMW1B and HMW2B are localized to the outer membrane and are required for the extracellular release of cognate structural proteins. The HMWB proteins also show low-level similarity to a series of outer membrane ushers involved in pilus biogenesis, including H. in£uenzae HifC [88], the Salmonella enteritidis SefC protein [119], and the E. coli CS6 usher called CssD. Like the ushers, HMW1B and HMW2B are predicted to form L-barrels, which might form pores that facilitate HMW1 and HMW2 translocation across the outer membrane.…”

Section: Hmw1 and Hmw2 Proteinsmentioning

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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“…Functional analysis of the various H. influenzae pilus genes has been based in part on homologies to their counterparts in other pilus systems [81, 86–88]. The initial identification of an 8‐kb fragment sufficient for pilus biogenesis led to the determination of the complete pilus gene cluster, which contains five genes designated hifA – hifE .…”

Section: Establishment On the Mucosal Surfacementioning

confidence: 99%

“…hifC encodes a protein with homology to pilus ushers, including PapC of the E. coli P pilus system, FimD of the type 1 pilus system, FimC of B. pertussis , and MrkC of K. pneumoniae [88]. Based on studies of PapC and FimD, ushers reside in the outer membrane and are believed to provide a structural platform for the ordered assembly of pilus subunits into the growing organelle.…”

Section: Establishment On the Mucosal Surfacementioning

confidence: 99%

Molecular determinants of the pathogenesis of disease due to non-typableHaemophilus influenzae

et al. 1999

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

Cited by 33 publications

References 36 publications

Secretion of the Haemophilus influenzae HMW1 and HMW2 adhesins involves a periplasmic intermediate and requires the HMWB and HMWC proteins

Secretion of the Haemophilus influenzae HMW1 and HMW2 adhesins involves a periplasmic intermediate and requires the HMWB and HMWC proteins

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

Molecular determinants of the pathogenesis of disease due to non-typableHaemophilus influenzae

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