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...

Full description

Saved in:
Bibliographic Details
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:
Online Access:https://www.mdpi.com/2076-3921/14/3/323
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850090365621633024
author 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
author_facet 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
author_sort Alessandra Scano
collection DOAJ
description 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.
format Article
id doaj-art-00aef80b579d45df8661e4525d64ebe7
institution DOAJ
issn 2076-3921
language English
publishDate 2025-03-01
publisher MDPI AG
record_format Article
series Antioxidants
spelling doaj-art-00aef80b579d45df8661e4525d64ebe72025-08-20T02:42:35ZengMDPI AGAntioxidants2076-39212025-03-0114332310.3390/antiox14030323Oxidative 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>Alessandra Scano0Sara Fais1Giuliana Ciappina2Martina Genovese3Barbara Granata4Monica Montopoli5Pierluigi Consolo6Patrizia Carroccio7Paola Muscolino8Alessandro Ottaiano9Alessia Bignucolo10Antonio Picone11Enrica Toscano12Germano Orrù13Massimiliano Berretta14Oral Biotechnology Laboratory (OBL), Department of Surgical Science, University of Cagliari, 09124 Cagliari, ItalyOral Biotechnology Laboratory (OBL), Department of Surgical Science, University of Cagliari, 09124 Cagliari, ItalyDivision of Medical Oncology, AOU “G. Martino” Hospital, University of Messina, 98124 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98122 Messina, ItalySchool of Specialization in Medical Oncology, Department of Human Pathology “G. Barresi”, University of Messina, 98125 Messina, ItalyDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padua, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98122 Messina, ItalySchool of Specialization in Medical Oncology, Department of Human Pathology “G. Barresi”, University of Messina, 98125 Messina, ItalySchool of Specialization in Medical Oncology, Department of Human Pathology “G. Barresi”, University of Messina, 98125 Messina, ItalyDivision of Innovative Therapies for Abdominal Metastases, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Naples, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98122 Messina, ItalyDivision of Medical Oncology, AOU “G. Martino” Hospital, University of Messina, 98124 Messina, ItalySchool of Specialization in Medical Oncology, Department of Human Pathology “G. Barresi”, University of Messina, 98125 Messina, ItalyOral Biotechnology Laboratory (OBL), Department of Surgical Science, University of Cagliari, 09124 Cagliari, ItalyDivision of Medical Oncology, AOU “G. Martino” Hospital, University of Messina, 98124 Messina, ItalyBackground: <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.https://www.mdpi.com/2076-3921/14/3/323<i>Fusobacterium nucleatum</i>colon-rectal canceroxidative stresspri-miRNAgene expression
spellingShingle 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
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>
Antioxidants
<i>Fusobacterium nucleatum</i>
colon-rectal cancer
oxidative stress
pri-miRNA
gene expression
title 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>
title_full 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>
title_fullStr 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>
title_full_unstemmed 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>
title_short 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>
title_sort 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
topic <i>Fusobacterium nucleatum</i>
colon-rectal cancer
oxidative stress
pri-miRNA
gene expression
url https://www.mdpi.com/2076-3921/14/3/323
work_keys_str_mv AT alessandrascano oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT sarafais oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT giulianaciappina oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT martinagenovese oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT barbaragranata oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT monicamontopoli oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT pierluigiconsolo oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT patriziacarroccio oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT paolamuscolino oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT alessandroottaiano oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT alessiabignucolo oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT antoniopicone oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT enricatoscano oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT germanoorru oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi
AT massimilianoberretta oxidativestressbyhsub2subosub2subasapotentialinductorintheswitchfromcommensaltopathogeninoncogenicbacteriumifusobacteriumnucleatumi