Dataset Information

Proteomic analysis of Filifactor alocis type and clinically isolated strains

ABSTRACT: Filifactor alocis is a Gram-positive asaccharolytic, obligate anaerobic rod of the phylum Firmicutes, strongly associated with periodontitis. In this study, we performed the whole proteomic analysis of an F. alocis type strain (ATCC 35896; CCUG 47790), as well as nine clinically isolated strains at the Clinical Oral Microbiology Laboratory, Umeå University, for identification and deeper characterization of this species. Label-free quantification was used to compare the proteomic differences between different strains.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Filifactor Alocis

SUBMITTER: Kai Bao

LAB HEAD: Nagihan Bostanci

PROVIDER: PXD026971 | Pride | 2022-06-09

REPOSITORIES: Pride

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Publications

Proteomic Characterization of the Oral Pathogen Filifactor alocis Reveals Key Inter-Protein Interactions of Its RTX Toxin: FtxA.

Bao Kai K Claesson Rolf R Gehrig Peter P Grossmann Jonas J Oscarsson Jan J Belibasakis Georgios N GN

Pathogens (Basel, Switzerland) 20220517 5

Filifactor alocis is a Gram-positive asaccharolytic, obligate anaerobic rod that has been isolated from a variety of oral infections including periodontitis, peri-implantitis, and odontogenic abscesses. As a newly emerging pathogen, its type strain has been investigated for pathogenic properties, yet little is known about its virulence variations among strains. We previously screened the whole genome of nine clinical oral isolates and a reference strain of F. alocis, and they expre ...[more]

PMID: 35631111

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Project description:The complex reservoir of metabolite-producing bacteria in the gastrointestinal tract contributes tremendously to human health and disease. Bacterial composition, and by extension gut metabolomic composition, is undoubtably influenced by the use of modern antibiotics. Herein, we demonstrate that polymyxin B, a last resort antibiotic used for chronic multidrug resistant infections infections, influences the production of the genotoxic metabolite colibactin from adherent-invasive Escherichia coli (AIEC) NC101. Colibactin can augment colorectal cancer (CRC) through DNA double stranded breaks and interstrand crosslinks. While the structure and biosynthesis of colibactin has been elucidated, chemical-induced regulation of its biosynthetic gene cluster and subsequent production of the genotoxin by pathogenic E. coli are largely unexplored. This research highlights the regulation of the colibactin-producing biosynthetic gene cluster under polymyxin stress. Using a multi-omic approach, we have identified that polymyxin stress enhances the abundance of colibactin biosynthesis proteins (Clb’s) in multiple pks+ E. coli strains, including pro-carcinogenic AIEC: NC101, the probiotic strain: E. coli Nissle 1917, and the antibiotic testing strain: E. coli ATCC 25922. Expression analysis via qPCR revealed that increased transcription of clb genes likely contributes to elevated Clb protein levels in NC101. Enhanced production of Clb’s by NC101 under polymyxin stress matched an increased production of the colibactin prodrug motif, a proxy for the mature genotoxic metabolite. Furthermore, E. coli with heightened tolerance for polymyxin antibiotics induced greater DNA damage, assessed by quantification of γH2AX staining in cultured intestinal epithelial cells. This study establishes a key link between the polymyxin B stress response and colibactin production in pks+ E. coli. Ultimately, our findings will inform future studies investigating colibactin regulation, the microbial response to antibiotics in the gut, and the ability of seemingly innocuous commensal microbes to induce host disease.

Dataset Information

Proteomic analysis of Filifactor alocis type and clinically isolated strains

Publications

Proteomic Characterization of the Oral Pathogen <i>Filifactor alocis</i> Reveals Key Inter-Protein Interactions of Its RTX Toxin: FtxA.

Similar Datasets

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