Dataset Information

Analysing the Structural Effect of Point Mutations of Cytotoxic Necrotizing Factor 1 (CNF1) on Lu/BCAM Adhesion Glycoprotein Association.

ABSTRACT: Cytotoxic Necrotizing Factor 1 (CNF1) was identified in 1983 as a protein toxin produced by certain pathogenic strains of Escherichia coli. Since then, numerous studies have investigated its particularities. For instance, it is associated with the single chain AB-toxin family, and can be divided into different functional and structural domains, e.g., catalytic and transmembrane domain and interaction sites. A few years ago, the identification of the Lutheran (Lu) adhesion glycoprotein/basal cell adhesion molecule (BCAM) as a cellular receptor for CNF1 provided new insights into the adhesion process of CNF1. Very recently, the Ig-like domain 2 of Lu/BCAM was confirmed as the main interaction site using protein-protein interaction and competition studies with various different mutants. Here, I present in silico approaches that precisely explain the impact of these mutations, leading to a better explanation of these experimental studies. These results can be used in the development of future antitoxin strategies.

SUBMITTER: de Brevern AG

PROVIDER: S-EPMC5869410 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Analysing the Structural Effect of Point Mutations of Cytotoxic Necrotizing Factor 1 (CNF1) on Lu/BCAM Adhesion Glycoprotein Association.

de Brevern Alexandre G AG

Toxins 20180313 3

Cytotoxic Necrotizing Factor 1 (CNF1) was identified in 1983 as a protein toxin produced by certain pathogenic strains of <i>Escherichia coli</i>. Since then, numerous studies have investigated its particularities. For instance, it is associated with the single chain AB-toxin family, and can be divided into different functional and structural domains, e.g., catalytic and transmembrane domain and interaction sites. A few years ago, the identification of the Lutheran (Lu) adhesion glycoprotein/bas ...[more]

PMID: 29533999

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Project description:Background:Many Escherichia coli strains are considered to be a component of the normal flora found in the human and animal intestinal tracts. While most E. coli strains are commensal, some strains encode virulence factors that enable the bacteria to cause intestinal and extra-intestinal clinically-relevant infections. Colibactin, encoded by a genomic island (pks island), and cytotoxic necrotizing factor (CNF), encoded by the cnf gene, are genotoxic and can modulate cellular differentiation, apoptosis and proliferation. Some commensal and pathogenic pks+ and cnf+ E. coli strains have been associated with inflammation and cancer in humans and animals. Results:In the present study, E. coli strains encoding colibactin and CNF were identified in macaque samples. We performed bacterial cultures utilizing rectal swabs and extra-intestinal samples from clinically normal macaques. A total of 239 E. coli strains were isolated from 266 macaques. The strains were identified biochemically and selected isolates were serotyped as O88:H4, O25:H4, O7:H7, OM:H14, and OM:H16. Specific PCR for pks and cnf1 gene amplification, and phylogenetic group identification were performed on all E. coli strains. Among the 239 isolates, 41 (17.2%) were pks+/cnf1-, 19 (7.9%) were pks-/cnf1+, and 31 (13.0%) were pks+/cnf1+. One hundred forty-eight (61.9%) E. coli isolates were negative for both genes (pks-/cnf1-). In total, 72 (30.1%) were positive for pks genes, and 50 (20.9%) were positive for cnf1. No cnf2+ isolates were detected. Both pks+ and cnf1+ E. coli strains belonged mainly to phylogenetic group B2, including B21. Colibactin and CNF cytotoxic activities were observed using a HeLa cell cytotoxicity assay in representative isolates. Whole genome sequencing of 10 representative E. coli strains confirmed the presence of virulence factors and antibiotic resistance genes in rhesus macaque E. coli isolates. Conclusions:Our findings indicate that colibactin- and CNF-encoding E. coli colonize laboratory macaques and can potentially cause clinical and subclinical diseases that impact macaque models.

Dataset Information

Analysing the Structural Effect of Point Mutations of Cytotoxic Necrotizing Factor 1 (CNF1) on Lu/BCAM Adhesion Glycoprotein Association.

Publications

Analysing the Structural Effect of Point Mutations of Cytotoxic Necrotizing Factor 1 (CNF1) on Lu/BCAM Adhesion Glycoprotein Association.

Similar Datasets

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