Genetic Determinants of Hydrogen Sulfide Biosynthesis in Fusobacterium nucleatum Are Required for Bacterial Fitness, Antibiotic Sensitivity, and Virulence Original paper
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Divine Aleru
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Microbes
Microbes
Microbes are microscopic organisms living in and on the human body, shaping health through digestion, vitamin production, and immune protection. When microbial balance is disrupted, disease can occur. This guide explains key microbe types—bacteria, viruses, fungi, protozoa, and archaea—plus major pathogenic and beneficial examples.
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Divine Aleru
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Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
This study explored the genetic determinants of hydrogen sulfide (H2S) biosynthesis in Fusobacterium nucleatum and their role in bacterial fitness, antibiotic susceptibility, and virulence. The researchers investigated the enzymes responsible for H2S production, focusing on the genes megL, cysK1, cysK2, and hly, and their contributions to bacterial survival, antibiotic resistance, and pathogenicity in vivo.
Who was studied?
The study used Fusobacterium nucleatum strain ATCC 23726, which was genetically manipulated to create mutants lacking specific H2S-producing enzymes. These mutants, along with the wild-type strain, were analyzed for growth, H2S production, antibiotic sensitivity, and virulence in a mouse model of preterm birth.
What were the most important findings?
The study identified MegL (L-methionine γ-lyase) as the major enzyme responsible for H2S production in F. nucleatum in vivo. Deletion of megL led to a significant reduction in H2S production, highlighting its critical role in both bacterial survival and virulence. Interestingly, although CysK1 is essential for cell viability and plays a role in H2S production, it is not a major contributor in vivo. The study also revealed that the megL mutant displayed altered antibiotic susceptibility, showing resistance to kanamycin and increased sensitivity to nalidixic acid. This suggests that MegL and H2S contribute to the bacteria’s tolerance to antibiotics. Furthermore, the megL mutant was attenuated in virulence in a mouse model of preterm birth, with significantly reduced colonization of the placenta and amniotic fluid compared to the wild-type strain. These findings underline the critical role of MegL in F. nucleatum’s pathogenicity and response to antibiotics.
What are the greatest implications of this study?
The study provides significant insights into the role of H2S and the MegL enzyme in the pathogenesis of Fusobacterium nucleatum. Understanding the genetic pathways of H2S production and its impact on bacterial fitness and virulence opens avenues for potential therapeutic interventions. Targeting MegL or the H2S production pathway could offer a novel strategy for reducing F. nucleatum’s virulence in infections such as preterm birth and colorectal cancer. Additionally, the findings suggest that modulation of H2S production may be a key factor in managing F. nucleatum‘s antibiotic resistance, offering new strategies for treating infections caused by this bacterium.
Fusobacterium nucleatum
Fusobacterium nucleatum is a Gram-negative, anaerobic bacterium commonly found in the oral cavity, where it plays a crucial role in the formation of biofilms. Beyond its presence in the mouth, Fn is implicated in a variety of systemic conditions, including periodontal disease, colorectal cancer, and inflammatory bowel disease. Known for its ability to coaggregate with other bacteria, Fn's pathogenic potential is magnified in dysbiotic microbial communities, making it a key player in polymicrobial infections. The bacterium utilizes multiple virulence factors such as FadA and Fap2, which facilitate adhesion to host tissues and immune evasion, ultimately contributing to its role in chronic and inflammatory diseases.