Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Ergebnis 18 von 448

Details

Autor(en) / Beteiligte
Titel
Deciphering the interplay between the genotoxic and probiotic activities of Escherichia coli Nissle 1917
Ist Teil von
  • PLoS pathogens, 2019-09, Vol.15 (9), p.e1008029
Ort / Verlag
United States: Public Library of Science
Erscheinungsjahr
2019
Quelle
MEDLINE
Beschreibungen/Notizen
  • Although Escherichia coli Nissle 1917 (EcN) has been used therapeutically for over a century, the determinants of its probiotic properties remain elusive. EcN produces two siderophore-microcins (Mcc) responsible for an antagonistic activity against other Enterobacteriaceae. EcN also synthesizes the genotoxin colibactin encoded by the pks island. Colibactin is a virulence factor and a putative pro-carcinogenic compound. Therefore, we aimed to decouple the antagonistic activity of EcN from its genotoxic activity. We demonstrated that the pks-encoded ClbP, the peptidase that activates colibactin, is required for the antagonistic activity of EcN. The analysis of a series of ClbP mutants revealed that this activity is linked to the transmembrane helices of ClbP and not the periplasmic peptidase domain, indicating the transmembrane domain is involved in some aspect of Mcc biosynthesis or secretion. A single amino acid substitution in ClbP inactivates the genotoxic activity but maintains the antagonistic activity. In an in vivo salmonellosis model, this point mutant reduced the clinical signs and the fecal shedding of Salmonella similarly to the wild type strain, whereas the clbP deletion mutant could neither protect nor outcompete the pathogen. The ClbP-dependent antibacterial effect was also observed in vitro with other E. coli strains that carry both a truncated form of the Mcc gene cluster and the pks island. In such strains, siderophore-Mcc synthesis also required the glucosyltransferase IroB involved in salmochelin production. This interplay between colibactin, salmochelin, and siderophore-Mcc biosynthetic pathways suggests that these genomic islands were co-selected and played a role in the evolution of E. coli from phylogroup B2. This co-evolution observed in EcN illustrates the fine margin between pathogenicity and probiotic activity, and the need to address both the effectiveness and safety of probiotics. Decoupling the antagonistic from the genotoxic activity by specifically inactivating ClbP peptidase domain opens the way to the safe use of EcN.
Sprache
Englisch
Identifikatoren
ISSN: 1553-7374, 1553-7366
eISSN: 1553-7374
DOI: 10.1371/journal.ppat.1008029
Titel-ID: cdi_plos_journals_2306340691
Format
Schlagworte
Amino acid substitution, Analgesics, Animals, Antibacterial agents, Antibiosis - genetics, Antibiosis - physiology, Bacteria, Bacteriocins - genetics, Bacteriocins - metabolism, Bacteriocins - toxicity, Biochemistry, Molecular Biology, Biology and Life Sciences, Biosynthesis, Biosynthetic Pathways - genetics, Carcinogens, Chemical properties, Coevolution, Colorectal cancer, Decoupling, Deletion mutant, Deoxyribonucleic acid, DNA, E coli, Earth Sciences, Enterobactin - analogs & derivatives, Enterobactin - genetics, Enterobactin - physiology, Enterobactin - toxicity, Escherichia coli, Escherichia coli - genetics, Escherichia coli - pathogenicity, Escherichia coli - physiology, Escherichia coli Proteins - chemistry, Escherichia coli Proteins - genetics, Escherichia coli Proteins - physiology, Evolution, Female, Genes, Bacterial, Genomic Islands, Genotoxicity, Glucosyltransferase, Health aspects, Helices, Humans, Life Sciences, Medicine and Health Sciences, Metabolites, Mice, Mice, Inbred C57BL, Microbiology and Parasitology, Models, Biological, Multigene Family, Mutagens - toxicity, Mutants, Mutation, Pathogenicity, Pathogens, Peptidase, Peptide Hydrolases - chemistry, Peptide Hydrolases - genetics, Peptide Hydrolases - physiology, Peptides, Peptides - genetics, Peptides - physiology, Peptides - toxicity, Polyketides - toxicity, Probiotics, Probiotics - therapeutic use, Probiotics - toxicity, Protein Domains, Salmonella, Salmonella Infections, Animal - microbiology, Salmonella Infections, Animal - therapy, Salmonella typhimurium, Salmonellosis, Siderophores - genetics, Siderophores - physiology, Siderophores - toxicity, Virulence, Virulence factors, Virulence Factors - genetics, Virulence Factors - physiology, Virulence Factors - toxicity

Weiterführende Literatur

Empfehlungen zum selben Thema automatisch vorgeschlagen von bX