A novel phase-variable autotransporter serine protease, AusI, of Neisseria meningitidis

Ulsen, Peter van; Adler, Ben; Fäßler, Peter E.; Gilbert, Maarten J.; Schilfgaarde, Muriel van; Ley, Peter van der; Alphen, Loek van; Tommassen, Jan

doi:10.1016/j.micinf.2006.03.007

Cited by 36 publications

(43 citation statements)

References 33 publications

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“…In addition to IgA protease, NalP also processes the autotransporters App and AusI (van Ulsen et al, 2003(van Ulsen et al, , 2006. The passenger of App also includes an a-peptide.…”

Section: Resultsmentioning

confidence: 99%

“…The differences in processing of IgA protease between N. meningitidis and N. gonorrhoeae can be explained only in part by the absence of a functional NalP in N. gonorrhoeae (van Ulsen et al, 2001;van Ulsen & Tommassen, 2006). Whilst this absence may explain why the linker peptide is not released from the b-core in the IgA protease of N. gonorrhoeae, it fails to explain the observation that the apeptide remained fused to the TD in nalP mutants of N. meningitidis.…”

Section: Variations In Autocatalytic Processing Of Iga Protease Betwementioning

confidence: 99%

“…For example, in the canonical autotransporter IgA protease of Neisseria gonorrhoeae, encoded by the iga gene, the secreted passenger domain is further processed into a protease domain (~106 kDa), a c-peptide (~3.1 kDa) and an a-peptide (4 5 kDa) (Pohlner et al, 1987). Similarly, our laboratory has shown that the passenger domains of the autotransporters App and AusI of Neisseria meningitidis consist of at least two subdomains (van Ulsen et al, 2003(van Ulsen et al, , 2006. The TDs may also consist of several subdomains, e.g.…”

Section: Introductionmentioning

confidence: 96%

“…In N. gonorrhoeae, which does not encode a functional NalP (van Ulsen et al, 2001;van Ulsen & Tommassen, 2006), the a-peptide of IgA protease was detected as a separate polypeptide in the extracellular medium (Pohlner et al, 1987). In N. meningitidis, the involvement of NalP may indicate different processing and the fate of Jose et al, 2000) in the a-peptide, one or two copies of the peptide [VSESVDTSDKQPQDNTELHEKYEN] in the linker and one to four copies of a tetra-peptide repeat ([QAAA] or [QAVA]) at the C terminus.…”

Section: Introductionmentioning

confidence: 99%

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Variable processing of the IgA protease autotransporter at the cell surface of Neisseria meningitidis

et al. 2014

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As with all classical monomeric autotransporters, IgA protease of Neisseria meningitidis is a modular protein consisting of an N-terminal signal sequence, a passenger domain and a Cterminal translocator domain (TD) that assists in the secretion of the passenger domain across the outer membrane. The passenger of IgA protease consists of three separate domains: the protease domain, the c-peptide and the a-peptide that contains nuclear localization signals (NLSs). The protease domain is released into the extracellular milieu either via autocatalytic processing or via cleavage by another autotransporter, NalP, expression of which is phase-variable. NalP-mediated cleavage results in the release of a passenger that includes the a-and c-peptides. Here, we studied the fate of the a-peptide when NalP was not expressed and observed strain-dependent differences. In meningococcal strains where the a-peptide contained a single NLS, the a-peptide remained covalently attached to the TD and was detected at the cell surface. In other strains, the a-peptide contained four NLSs and was separated from the TD by an IgA protease autoproteolytic cleavage site. In many of those cases, the a-peptide was found non-covalently associated with the cells as a separate polypeptide. The cell surface association of the a-peptides may be relevant physiologically. We report a novel function for the a-peptide, i.e. the binding of heparin -an immune-modulatory molecule that in the host is found in the extracellular matrix and connected to cell surfaces.

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“…In addition to IgA protease, NalP also processes the autotransporters App and AusI (van Ulsen et al, 2003(van Ulsen et al, , 2006. The passenger of App also includes an a-peptide.…”

Section: Resultsmentioning

confidence: 99%

Section: Variations In Autocatalytic Processing Of Iga Protease Betwementioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Variable processing of the IgA protease autotransporter at the cell surface of Neisseria meningitidis

et al. 2014

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“…IcsA for instance, an autotransporter of Shigella flexneri, is cleaved by a dedicated outer membrane protease called IcsP, which is related to the OmpT protease found in E. coli (21). Similarly, the Neisseria meningitidis serine protease NalP is specifically responsible for the partial processing of various autotransporters, including the IgA protease (22), App (22), AusI (23), and MspA (24). In contrast, the cleavage of AIDA-I is not mediated by the known E. coli periplasmic or outer membrane proteases (DegP, OmpT, or OmpP), and it occurs in E. coli as well as in Shigella or Salmonella strains (19).…”

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confidence: 99%

Autoprocessing of the Escherichia coli AIDA-I Autotransporter

Charbonneau

Janvore²,

Mourez

2009

Journal of Biological Chemistry

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The cleavage of the autotransporter adhesin involved in diffuse adherence (AIDA-I) of Escherichia coli yields a membraneembedded fragment, AIDAc, and an extracellular fragment, the mature AIDA-I adhesin. The latter remains noncovalently associated with AIDAc but can be released by heat treatment. In this study we determined the mechanism of AIDA-I cleavage. We showed that AIDA-I processing is an autocatalytic event by monitoring the in vitro cleavage of an uncleaved mutant protein isolated from inclusion bodies. Furthermore, by following changes in circular dichroism spectra and protease resistance of the renaturated protein, we showed that the cleavage of the protein is correlated with folding. With site-directed deletions, we showed that the catalytic activity of the protein lies in a region encompassing amino acids between Ala-667 and Thr-953, which includes the conserved junction domain of some autotransporters. With site-directed point mutations, we also found that Asp-878 and Glu-897 are involved in the processing of AIDA-I and that a mutation preserving the acidic side chain of Asp-878 was tolerated, giving evidence that this carboxylic acid group is directly involved in catalysis. Last, we confirmed that cleavage of AIDA-I is intramolecular. Our results unveil a new mechanism of auto-processing in the autotransporter family.Monomeric autotransporters, secreted by the type Va secretion pathway, constitute one of the largest family of secreted proteins in Gram-negative bacteria (1). Various virulence attributes have been associated with most autotransporters, such as adhesion or invasion, self-association, biofilm formation, serum resistance, and cytotoxic activity to name just a few (2, 3). Autotransporters are synthesized as pre-proproteins with modular organizations. An N-terminal sec-dependent signal sequence permits the secretion of the protein across the inner membrane (4). A C-terminal membrane-embedded domain promotes secretion of parts of the protein across the outer membrane and is composed of a ␤-barrel and a ␣-helix spanning its lumen (5, 6). The central domain of the protein is, thus, extracellular and bears its functional part. In some cases the extracellular part of the protein is cleaved and remains associated with the outer membrane or is secreted in the extracellular milieu. Directly preceding the membrane-embedded domain, a functional subdomain of ϳ100 amino acids is sometimes present in the extracellular domain and has been called the junction region (also named autochaperone domain or stable core) (7-9). This region is essential for stabilizing the ␤-barrel and/or to promote folding of the extracellular domain (7-9).The adhesin involved in diffuse adherence (AIDA-I) 3 is a monomeric autotransporter that has been extensively studied. AIDA-I was originally identified as a plasmid-encoded protein from a diffusely adhering Escherichia coli strain isolated in a case of infantile diarrhea (10). This adhesin was then shown to play a role in neonatal and postweaning diarrheal diseases in pigle...

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An Overview of Neisseria meningitidis

Hollingshead

Tang

2019

Methods in Molecular Biology

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Methods in Molecular Biology Introductory Overview Overview of Neisseria meningitidisNeisseria meningitidis, or the meningococcus, is a Gram negative, non-motile diplococcus that can cause septicaemia and meningitis in susceptible individuals. It is closely related to N. gonorrhoeae, or the gonococcus, which is the causative agent of the sexually transmitted infection gonorrhoea. N. meningitidis and N. gonorrhoeae are the only pathogenic members of the genus Neisseria, which includes several commensal species 1 . Both N. meningitdis and N. gonorrhoeae are obligate human pathogens. N. meningitidis is acquired through person-to-person contact via aerosols and oral or nasal secretions and is a member of the normal nasopharyngeal microbiome in healthy individuals. Once acquired, the meningococcus may be carried transiently or for a period of several months before carriage is lost. Carriage studies have shown N. meningitidis resides in 3-35% of the population depending on geographic location, climate and local disease status 2 . N. meningitidis is considered an accidental pathogen, as the bacterium only rarely crosses into the bloodstream causing life-threatening diseases such as septicaemia and meningitis. Meningococcal disease occurs endemically as sporadic cases in a community, or in epidemics, such as those observed in the African meningitis belt. The most susceptible individuals are infants under 1 year of age, teenagers and young adults 3,4 . Others at risk from meningoccal disease are those with deficiencies in their complement system and asplenia 4 . The onset of disease is rapid and case fatality rates range between 10-20%, despite the availability of antibiotic treatment. Of the survivors, 10-20% develop long-term sequelae, including hearing loss, loss of limbs, skin scarring and neurodevelopmental deficits, and up to 36% develop deficits in physical, cognitive or psychological functioning 5, 6 .

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A novel phase-variable autotransporter serine protease, AusI, of Neisseria meningitidis

Cited by 36 publications

References 33 publications

Variable processing of the IgA protease autotransporter at the cell surface of Neisseria meningitidis

Variable processing of the IgA protease autotransporter at the cell surface of Neisseria meningitidis

Autoprocessing of the Escherichia coli AIDA-I Autotransporter

An Overview of Neisseria meningitidis

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