Perturbed human sub-networks by Fusobacterium nucleatum candidate virulence proteins

• Published in: Microbiome Vol. 5; no. 1; pp. 89 - 17
• Main Authors: Zanzoni, Andreas, Spinelli, Lionel, Braham, Shérazade, Brun, Christine
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.08.2017; BioMed Central; BMC
• Subjects: Bacterial Proteins - isolation & purification; Bacterial Proteins - metabolism; Bacterial Proteins - secretion; Bioinformatics; Colorectal cancer; Colorectal Neoplasms - microbiology; Colorectal Neoplasms - physiopathology; Computers, Molecular; Databases, Genetic; Development and progression; Female; Fusobacterium Infections - microbiology; Fusobacterium Infections - physiopathology; Fusobacterium nucleatum; Fusobacterium nucleatum - chemistry; Fusobacterium nucleatum - pathogenicity; Gastrointestinal diseases; Gene Regulatory Networks; Gram-negative bacteria; Host-Pathogen Interactions - genetics; Humans; Inflammatory Bowel Diseases - microbiology; Inflammatory Bowel Diseases - physiopathology; Interaction network; Life Sciences; Male; Middle Aged; Molecular mimicry; Proteins; Quantitative Methods; Secretome; Short linear motifs; Signal Transduction - genetics; Virulence (Microbiology); Virulence Factors - genetics; Inflammatory bowel diseases; Fusobacterium nucleatum; Colorectal cancer; Interaction network; Short linear motifs; Molecular mimicry; Secretome; Bioinformatics; Virulence proteins
• ISSN: 2049-2618; 2049-2618
• DOI: 10.1186/s40168-017-0307-1

Fusobacterium nucleatum is a gram-negative anaerobic species residing in the oral cavity and implicated in several inflammatory processes in the human body. Although F. nucleatum abundance is increased in inflammatory bowel disease subjects and is prevalent in colorectal cancer patients, the causal role of the bacterium in gastrointestinal disorders and the mechanistic details of host cell functions subversion are not fully understood. We devised a computational strategy to identify putative secreted F. nucleatum proteins (FusoSecretome) and to infer their interactions with human proteins based on the presence of host molecular mimicry elements. FusoSecretome proteins share similar features with known bacterial virulence factors thereby highlighting their pathogenic potential. We show that they interact with human proteins that participate in infection-related cellular processes and localize in established cellular districts of the host-pathogen interface. Our network-based analysis identified 31 functional modules in the human interactome preferentially targeted by 138 FusoSecretome proteins, among which we selected 26 as main candidate virulence proteins, representing both putative and known virulence proteins. Finally, six of the preferentially targeted functional modules are implicated in the onset and progression of inflammatory bowel diseases and colorectal cancer. Overall, our computational analysis identified candidate virulence proteins potentially involved in the F. nucleatum-human cross-talk in the context of gastrointestinal diseases.