Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection control
Clostridioides difficile is a major cause of nosocomial diarrhea. As current antibiotic treatment failures and recurrence of infections are highly frequent, alternative strategies are needed for the treatment of this disease. This study explores the use of bacteriocins, specifically lacticin 3147 an...
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2451081 |
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| author | Natalia S. Ríos Colombo R. Paul Ross Colin Hill |
| author_facet | Natalia S. Ríos Colombo R. Paul Ross Colin Hill |
| author_sort | Natalia S. Ríos Colombo |
| collection | DOAJ |
| description | Clostridioides difficile is a major cause of nosocomial diarrhea. As current antibiotic treatment failures and recurrence of infections are highly frequent, alternative strategies are needed for the treatment of this disease. This study explores the use of bacteriocins, specifically lacticin 3147 and pediocin PA-1, which have reported inhibitory activity against C. difficile. We engineered Lactococcus lactis strains to produce these bacteriocins individually or in combination, aiming to enhance their activity against C. difficile. Our results show that lacticin 3147 and pediocin PA-1 display synergy, resulting in higher anti-C. difficile activity. We then evaluated the effects of these L. lactis strains in a Simplified Human Intestinal Microbiome (SIHUMI-C) model, a bacterial consortium of eight diverse human gut species that includes C. difficile. After introducing the bacteriocin-producing L. lactis strains into SIHUMI-C, samples were collected over 24 hours, and the genome copies of each species were assessed using qPCR. Contrary to expectations, the combined bacteriocins increased C. difficile levels in the consortium despite showing synergy against C. difficile in agar-based screening. This can be rationally explained by antagonistic inter-species interactions within SIHUMI-C, providing new insights into how broad-spectrum antimicrobials might fail to control targeted species in complex gut microbial communities. These findings highlight the need to mitigate off-target effects in complex gut microbiomes when developing bacteriocin-based therapies with potential clinical implications for infectious disease treatment. |
| format | Article |
| id | doaj-art-cd9eb17322e74ff9a76def2d0c85bf98 |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-cd9eb17322e74ff9a76def2d0c85bf982025-01-16T11:04:21ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2451081Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection controlNatalia S. Ríos Colombo0R. Paul Ross1Colin Hill2APC Microbiome Ireland, University College Cork, Cork, IrelandAPC Microbiome Ireland, University College Cork, Cork, IrelandAPC Microbiome Ireland, University College Cork, Cork, IrelandClostridioides difficile is a major cause of nosocomial diarrhea. As current antibiotic treatment failures and recurrence of infections are highly frequent, alternative strategies are needed for the treatment of this disease. This study explores the use of bacteriocins, specifically lacticin 3147 and pediocin PA-1, which have reported inhibitory activity against C. difficile. We engineered Lactococcus lactis strains to produce these bacteriocins individually or in combination, aiming to enhance their activity against C. difficile. Our results show that lacticin 3147 and pediocin PA-1 display synergy, resulting in higher anti-C. difficile activity. We then evaluated the effects of these L. lactis strains in a Simplified Human Intestinal Microbiome (SIHUMI-C) model, a bacterial consortium of eight diverse human gut species that includes C. difficile. After introducing the bacteriocin-producing L. lactis strains into SIHUMI-C, samples were collected over 24 hours, and the genome copies of each species were assessed using qPCR. Contrary to expectations, the combined bacteriocins increased C. difficile levels in the consortium despite showing synergy against C. difficile in agar-based screening. This can be rationally explained by antagonistic inter-species interactions within SIHUMI-C, providing new insights into how broad-spectrum antimicrobials might fail to control targeted species in complex gut microbial communities. These findings highlight the need to mitigate off-target effects in complex gut microbiomes when developing bacteriocin-based therapies with potential clinical implications for infectious disease treatment.https://www.tandfonline.com/doi/10.1080/19490976.2025.2451081C. difficilebacteriocinmicrobiomelantibioticpediocin PA-1lacticin 3147 |
| spellingShingle | Natalia S. Ríos Colombo R. Paul Ross Colin Hill Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection control Gut Microbes C. difficile bacteriocin microbiome lantibiotic pediocin PA-1 lacticin 3147 |
| title | Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection control |
| title_full | Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection control |
| title_fullStr | Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection control |
| title_full_unstemmed | Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection control |
| title_short | Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection control |
| title_sort | synergistic and off target effects of bacteriocins in a simplified human intestinal microbiome implications for clostridioides difficile infection control |
| topic | C. difficile bacteriocin microbiome lantibiotic pediocin PA-1 lacticin 3147 |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2451081 |
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