Oxidative Stress by H<sub>2</sub>O<sub>2</sub> as a Potential Inductor in the Switch from Commensal to Pathogen in Oncogenic Bacterium <i>Fusobacterium nucleatum</i>

Oxidative Stress by H<sub>2</sub>O<sub>2</sub> as a Potential Inductor in the Switch from Commensal to Pathogen in Oncogenic Bacterium <i>Fusobacterium nucleatum</i>

Background: <i>Fusobacterium nucleatum</i> is a pathobiont that plays a dual role as both a commensal and a pathogen. The oral cavity typically harbors this anaerobic, Gram-negative bacterium. At the same time, it is closely linked to colorectal cancer due to its potential involvement in...

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Main Authors: Alessandra Scano, Sara Fais, Giuliana Ciappina, Martina Genovese, Barbara Granata, Monica Montopoli, Pierluigi Consolo, Patrizia Carroccio, Paola Muscolino, Alessandro Ottaiano, Alessia Bignucolo, Antonio Picone, Enrica Toscano, Germano Orrù, Massimiliano Berretta
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Antioxidants
Subjects:
<i>Fusobacterium nucleatum</i>
colon-rectal cancer
oxidative stress
pri-miRNA
gene expression
Online Access:https://www.mdpi.com/2076-3921/14/3/323
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Summary:Background: <i>Fusobacterium nucleatum</i> is a pathobiont that plays a dual role as both a commensal and a pathogen. The oral cavity typically harbors this anaerobic, Gram-negative bacterium. At the same time, it is closely linked to colorectal cancer due to its potential involvement in tumor progression and resistance to chemotherapy. The mechanism by which it transforms from a commensal to a pathogen remains unknown. For this reason, we investigated the role of oxidative status as an initiatory factor in changing the bacterium’s pathogenicity profile. Methods: A clinical strain of <i>F. nucleatum</i> subsp. <i>animalis</i> biofilm was exposed to different oxidative stress levels through varying subinhibitory amounts of H<sub>2</sub>O<sub>2</sub>. Subsequently, we investigated the bacterium’s behavior in vitro by infecting the HT-29 cell line. We evaluated bacterial colonization, volatile sulfur compounds production, and the infected cell’s oxidative status by analyzing <i>HMOX1</i>, <i>pri-miRNA 155</i>, and <i>146a</i> gene expression. Results: The bacterial colonization rate, dimethyl sulfide production, and <i>pri-miRNA 155</i> levels all increased when stressed bacteria were used, suggesting a predominant pathogenic function of these strains. Conclusions: The response of <i>F. nucleatum</i> to different oxidative conditions could potentially explain the increase in its pathogenic traits and the existence of environmental factors that may trigger the bacterium’s pathogenicity and virulence.
ISSN:2076-3921

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