<i>Neisseria meningitidis</i> App, a new adhesin with autocatalytic serine protease activity

Serruto, Davide; Adu‐Bobie, Jeannette; Scarselli, María; Veggi, Daniele; Pizza, Mariagrazia; Rappuoli, Rino; Aricò, Beatrice

doi:10.1046/j.1365-2958.2003.03420.x

Cited by 91 publications

(101 citation statements)

References 32 publications

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“…There is scarce evidence regarding their adhesin activity, specifically in directing attachment of bacteria to epithelial cells. For example, the protein App, produced by Neisseria meningitidis, is a determinant of adherence capacity to Chang cells (30). On the other hand, RpeA and Hap produced by rabbit enteropathogenic E. coli and Haemophilus influenzae, respectively, are able to direct adherence to epithelial cells when they are expressed in nonadherent strains of their respective species (31,32).…”

Section: Discussionmentioning

confidence: 99%

TleA, a Tsh-Like Autotransporter Identified in a Human Enterotoxigenic Escherichia coli Strain

et al. 2015

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e Enterotoxigenic Escherichia coli (ETEC), a leading cause of acute diarrhea, colonizes the intestine by means of adhesins. However, 15 to 50% of clinical isolates are negative for known adhesins, making it difficult to identify antigens for broad-coverage vaccines. The ETEC strain 1766a, obtained from a child with watery diarrhea in Chile, harbors the colonization factor CS23 but is negative for other known adhesins. One clone, derived from an ETEC 1766a genomic library (clone G10), did not produce CS23 yet was capable of adhering to Caco-2 cells. The goal of this study was to identify the gene responsible for this capacity. Random transposon-based mutagenesis allowed the identification of a 4,110-bp gene that codes for a homologue of the temperature-sensitive hemagglutinin (Tsh) autotransporter described in avian E. coli strains (97% identity, 90% coverage) and that is called TleA (Tsh-like ETEC autotransporter) herein. An isogenic ETEC 1766a strain with a tleA mutation showed an adhesion level similar to that of the wild-type strain, suggesting that the gene does not direct attachment to Caco-2 cells. However, expression of tleA conferred the capacity for adherence to nonadherent E. coli HB101. This effect coincided with the detection of TleA on the surface of nonpermeabilized bacteria, while, conversely, ETEC 1766a seems to secrete most of the produced autotransporter to the medium. On the other hand, TleA was capable of degrading bovine submaxillary mucin and leukocyte surface glycoproteins CD45 and P-selectin glycoprotein ligand 1 (PSGL-1). These results suggest that TleA promotes colonization of the intestinal epithelium and that it may modulate the host immune response.

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Section: Discussionmentioning

confidence: 99%

TleA, a Tsh-Like Autotransporter Identified in a Human Enterotoxigenic Escherichia coli Strain

et al. 2015

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“…For IgA1, Hap, and, more recently, App, it has been demonstrated that the cleavage was the result of an autoprocessing event involving the integral serine protease active sites of the autotransporter, present in the passenger domain (206,401,445). AIDA-I is also thought to be autoprocessed, although no serine protease motif has been found (472).…”

Section: Autotransporter Secretion Pathway (Type Va)mentioning

confidence: 99%

“…The outer membrane-localized precursor is surface accessible, and antibodies raised against recombinant App exhibit bactericidal activity against the homologous strain (182). Recently, Serruto et al (445) have confirmed that App is an important virulence determinant, which mediates adhesion to epithelial cells (but not endothelial cells). Indeed, App is the first nonpilus protein to be shown to possess adhesive properties in the presence of the polysaccharide capsule.…”

Section: N Meningitidis App and Mspa Autotransporter Proteinsmentioning

confidence: 99%

Type V Protein Secretion Pathway: the Autotransporter Story

Henderson

Navarro-Garcı́a

Desvaux

et al. 2004

Microbiol Mol Biol Rev

713

795

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Gram-negative bacteria possess an outer membrane layer which constrains uptake and secretion of solutes and polypeptides. To overcome this barrier, bacteria have developed several systems for protein secretion. The type V secretion pathway encompasses the autotransporter proteins, the two-partner secretion system, and the recently described type Vc or AT-2 family of proteins. Since its discovery in the late 1980s, this family of secreted proteins has expanded continuously, due largely to the advent of the genomic age, to become the largest group of secreted proteins in gram-negative bacteria. Several of these proteins play essential roles in the pathogenesis of bacterial infections and have been characterized in detail, demonstrating a diverse array of function including the ability to condense host cell actin and to modulate apoptosis. However, most of the autotransporter proteins remain to be characterized. In light of new discoveries and controversies in this research field, this review considers the autotransporter secretion process in the context of the more general field of bacterial protein translocation and exoprotein function

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“…Genome mining to investigate meningococcal autotransporters from whole-genome sequences identified several minor adhesion proteins: App (39), NhhA (36,40), MspA (52), and TspA (30). In addition, NadA has also been identified as an adhesion and invasion factor in human epithelial cells (5).…”

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confidence: 99%

Meningococcal Internalization into Human Endothelial and Epithelial Cells Is Triggered by the Influx of Extracellular l -Glutamate via GltT l -Glutamate ABC Transporter in Neisseria meningitidis

2011

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Meningococcal internalization into human cells is likely to be a consequence of meningococcal adhesion to human epithelial and endothelial cells. Here, we identified three transposon mutants of Neisseria meningitidis that were primarily defective in the internalization of human brain microvascular endothelial cells (HBMEC), with insertions occurring in the gltT (a sodium-independent L-glutamate transporter) gene or its neighboring gene, NMB1964 (unknown function). NMB1964 was tentatively named gltM in this study because of the presence of a mammalian cell entry (MCE)-related domain in the deduced amino acid sequences. The null ⌬gltT-⌬gltM N. meningitidis mutant was also defective in the internalization into human umbilical vein endothelial cells and the human lung carcinoma epithelial cell line A549, and the defect was suppressed by transcomplementation of the mutants with gltT ؉ -gltM ؉ genes. The intracellular survival of the ⌬gltT-⌬gltM mutant in HBMEC was not largely different from that of the wild-type strain under our experimental conditions. Introduction of a1-bp deletion and amber or ochre mutations in gltT-gltM genes resulted in the loss of efficient internalization into HBMEC. The defect in meningococcal internalization into HBMEC and L-glutamate uptake in the ⌬gltT-⌬gltM mutant were suppressed only in strains expressing both GltT and GltM proteins. The efficiency of meningococcal invasion to HBMEC decreased under L-glutamate-depleted conditions. Furthermore, ezrin, a key membrane-cytoskeleton linker, accumulated beneath colonies of the gltT ؉ -gltM ؉ N. meningitidis strain but not of the ⌬gltT-⌬gltM mutant. These findings suggest that L-glutamate influx via the GltT-GltM L-glutamate ABC transporter serves as a cue for N. meningitidis internalization into host cells.

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Neisseria meningitidis App, a new adhesin with autocatalytic serine protease activity

Cited by 91 publications

References 32 publications

TleA, a Tsh-Like Autotransporter Identified in a Human Enterotoxigenic Escherichia coli Strain

TleA, a Tsh-Like Autotransporter Identified in a Human Enterotoxigenic Escherichia coli Strain

Type V Protein Secretion Pathway: the Autotransporter Story

Meningococcal Internalization into Human Endothelial and Epithelial Cells Is Triggered by the Influx of Extracellular l -Glutamate via GltT l -Glutamate ABC Transporter in Neisseria meningitidis

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