Virulence Functions of Autotransporter Proteins

Henderson, Ian R.; Nataro, James P.

doi:10.1128/iai.69.3.1231-1243.2001

Cited by 390 publications

(355 citation statements)

References 165 publications

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“…Conserved aspartic acid, histidine, and serine residues were also present although, as exemplified by the PrtS homologues, Ssp-H1 and Ssp-H2, the presence of a potential serine protease catalytic triad does not necessarily imply that the protein will exhibit serine protease activity. Furthermore, the natural substrate(s) and biological significance of the S. marcescens secreted proteases are yet to be determined (14).…”

Section: Discussionmentioning

confidence: 99%

“…AutB is probably a pseudogene (2). The autotransporter mechanism of protein transportation and secretion was first described for the immunoglobulin A1 (IgA1) proteases of pathogenic Neisseria (26) and is a rapidly expanding family of proteins (14,15). The characteristic structure of autotransporter proteins and the secretion mechanism have been reviewed elsewhere (15,17).…”

mentioning

confidence: 99%

“…Autotransporter proteins, possessing a diverse array of N-terminal "functional" domains, have been reported in many gram-negative organisms (1,2,5,6,9,10,12,13,(23)(24)(25)(29)(30)(31). Typically, these proteins exhibit virulence-associated functions, such as adhesion, cytotoxicity, serum resistance, and proteolysis (14). Several organisms (e.g., Bordetella pertussis, Escherichia coli, and Haemophilus influenzae) are now recognized to produce an array of autotransporter proteins.…”

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confidence: 99%

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Autotransported Serine Protease A of Neisseria meningitidis : an Immunogenic, Surface-Exposed Outer Membrane, and Secreted Protein

2002

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Several autotransporter proteins have previously been identified in Neisseria meningitidis. Using molecular features common to most members of the autotransporter family of proteins, we have identified an additional novel ca. 112-kDa autotransporter protein in the meningococcal genomic sequence data. This protein, designated autotransported serine protease A (AspA), has significant N-terminal homology to the secreted serine proteases (subtilases) from several organisms and contains a serine protease catalytic triad. The amino acid sequence of AspA is well-conserved in serogroup A, B, and C meningococci. In Neisseria gonorrhoeae, the AspA homologue appears to be a pseudogene. The gene encoding AspA was cloned and expressed from meningococcal strain MC58 (B15:P1.16b). Anti-AspA antibodies were detected in patients' convalescent-phase sera, suggesting that AspA is expressed in vivo during infection and is immunogenic and cross-reactive. Rabbit polyclonal monospecific anti-AspA serum was used to probe whole-cell proteins from a panel of wild-type meningococcal strains and two AspA mutant strains. Expression of the ca. 112-kDa precursor polypeptide was detected in 12 of 20 wild-type meningococcal strains examined, suggesting that AspA expression is phase variable. Immunogold electron microscopy and cellular fractionation studies showed that the AspA precursor is transported to the outer membrane and remains surface exposed. Western blot experiments confirmed that smaller, ca. 68-or 70-kDa components of AspA (AspA68 and AspA70, respectively) are then secreted into the meningococcal culture supernatant. Site-directed mutagenesis of S426 abolished secretion of both rAspA68 and rAspA70 in Escherichia coli, confirming that AspA is an autocleaved autotransporter protein. In conclusion, we characterized a novel, surface-exposed and secreted, immunogenic, meningococcal autotransporter protein.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Autotransported Serine Protease A of Neisseria meningitidis : an Immunogenic, Surface-Exposed Outer Membrane, and Secreted Protein

2002

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“…AT proteins are found across many species of pathogenic Gram-negative bacteria, including Escherichia coli, Bordetella pertussis, Yersinia pestis, Helicobacter pylori, Pseudomonas aeruginosa, and Neissera, and are often associated with virulence. 4 Each AT…”

Section: Introductionmentioning

confidence: 99%

A conserved stable core structure in the passenger domain β‐helix of autotransporter virulence proteins

Renn

Clark

2008

Biopolymers

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In Gram‐negative bacteria, a wide variety of virulence factors are secreted via the autotransporter (AT) pathway. Intriguingly, there is no significant concentration of ATP in the periplasm, nor a proton gradient across the OM, so the energetic origin of efficient secretion of AT proteins is unknown. More than 97% of AT proteins are predicted to contain right‐handed parallel β‐helical structure, and the three crystal structures available for AT passenger domains each contain a long right‐handed parallel β‐helix. Previous studies have shown that pertactin, an AT from Bordetella pertussis, exhibits three‐state folding and has a C‐terminal stable core structure. Here, we show that Pet, an unrelated AT from Escherichia coli, also exhibits three‐state unfolding and also has a stable core structure. Deletion mutants, mass spectrometry, and N‐terminal sequencing demonstrate that the Pet stable core is also located near the C‐terminus of the passenger domain. Moreover, sequence analysis suggests that three‐state folding and a C‐terminal stable core structure could be important general features of the biogenesis of AT proteins in vivo. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 420–427, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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“…AF081494) and named bap5 (Blackburn, 2000), but later submitted independently as bapC (AJ277634). The protein BapC, like pertactin, Vag8, BrkA and TcfA, is a member of the bordetella autotransporter family (Henderson & Nataro, 2001), and is therefore a potential virulence factor and protective antigen. In addition to its possible use as a component of future ACVs, adenylate cyclase toxin (CyaA), is being investigated for use in multipurpose vaccines, by exploiting its ability to deliver foreign epitopes to antigen-presenting cells (Ladant & Ullmann, 1999).…”

Section: Introductionmentioning

confidence: 99%

Sequence variation and conservation in virulence-related genes of Bordetella pertussis isolates from the UK

Packard

Parton

Coote

et al. 2004

Journal of Medical Microbiology

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To determine the value of gene markers for surveillance and to assess the genetic stability of potential acellular pertussis vaccine components, the sequence variation in ten virulence-related genes of Bordetella pertussis was investigated in strains isolated in the UK between 1920 and 2002. These genes encode: pertactin (prnA); pertussis toxin subunits S1 (ptxA) and S3 (ptxC); tracheal colonization factor (tcfA); bordetella autotransporter protein C (bapC); bordetella resistance to killing protein (brkA); fimbrial antigen 2 (fim2); outer-membrane protein Q (ompQ); virulence-activated gene 8 (vag8) and adenylate cyclase toxin (cyaA). The encoded proteins are either components of current acellular vaccines (ACVs), or potential virulence markers for B. pertussis. Three strains used in the pertussis UK whole-cell vaccine (WCV), strain Tohama-I used for production of ACV components and the type strain of B. pertussis (18323 T ) were also analysed. Several novel alleles were found. The UK isolates were assigned multi-locus sequence types (MLSTs) according to a previously described scheme for B. pertussis based on three of these genes (ptxA, ptxC and tcfA). Compared with isolates from other countries, the UK clinical strains showed a distinct distribution of MLSTs. Apart from one strain that was MLST-3, all other recent isolates (2000)(2001)(2002) were identified as MLST-5. These isolates differed from the three WCV strains, which were MLST-2 or MLST-3, the Tohama-I strain (MLST-2) and the type strain of B. pertussis (MLST-9). MLST-3 and MLST-5 differ only by a single synonymous mutation, but this method does indicate that currently circulating strains of B. pertussis are not identical to the vaccine types, and they may differ in other important characteristics. Two new MLSTs were identified amongst historical UK isolates. Sequence-based typing offers a convenient method of analysing and comparing populations of B. pertussis from different time periods and from different countries. The variation exhibited by prnA and fim2 suggests that they could be useful, additional epidemiological markers in such a typing scheme.

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Virulence Functions of Autotransporter Proteins

Cited by 390 publications

References 165 publications

Autotransported Serine Protease A of Neisseria meningitidis : an Immunogenic, Surface-Exposed Outer Membrane, and Secreted Protein

Autotransported Serine Protease A of Neisseria meningitidis : an Immunogenic, Surface-Exposed Outer Membrane, and Secreted Protein

A conserved stable core structure in the passenger domain β‐helix of autotransporter virulence proteins

Sequence variation and conservation in virulence-related genes of Bordetella pertussis isolates from the UK

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