Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvae
Multiple gut antimicrobial mechanisms are coordinated in space and time to efficiently fight foodborne pathogens. In Drosophila melanogaster, production of reactive oxygen species (ROS) and antimicrobial peptides (AMPs) together with intestinal cell renewal play a key role in eliminating gut microbe...
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eLife Sciences Publications Ltd
2024-11-01
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| Online Access: | https://elifesciences.org/articles/98716 |
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| author | Fatima Tleiss Martina Montanari Romane Milleville Olivier Pierre Julien Royet Dani Osman Armel Gallet C Leopold Kurz |
| author_facet | Fatima Tleiss Martina Montanari Romane Milleville Olivier Pierre Julien Royet Dani Osman Armel Gallet C Leopold Kurz |
| author_sort | Fatima Tleiss |
| collection | DOAJ |
| description | Multiple gut antimicrobial mechanisms are coordinated in space and time to efficiently fight foodborne pathogens. In Drosophila melanogaster, production of reactive oxygen species (ROS) and antimicrobial peptides (AMPs) together with intestinal cell renewal play a key role in eliminating gut microbes. A complementary mechanism would be to isolate and treat pathogenic bacteria while allowing colonization by commensals. Using real-time imaging to follow the fate of ingested bacteria, we demonstrate that while commensal Lactiplantibacillus plantarum freely circulate within the intestinal lumen, pathogenic strains such as Erwinia carotovora or Bacillus thuringiensis, are blocked in the anterior midgut where they are rapidly eliminated by antimicrobial peptides. This sequestration of pathogenic bacteria in the anterior midgut requires the Duox enzyme in enterocytes, and both TrpA1 and Dh31 in enteroendocrine cells. Supplementing larval food with hCGRP, the human homolog of Dh31, is sufficient to block the bacteria, suggesting the existence of a conserved mechanism. While the immune deficiency (IMD) pathway is essential for eliminating the trapped bacteria, it is dispensable for the blockage. Genetic manipulations impairing bacterial compartmentalization result in abnormal colonization of posterior midgut regions by pathogenic bacteria. Despite a functional IMD pathway, this ectopic colonization leads to bacterial proliferation and larval death, demonstrating the critical role of bacteria anterior sequestration in larval defense. Our study reveals a temporal orchestration during which pathogenic bacteria, but not innocuous, are confined in the anterior part of the midgut in which they are eliminated in an IMD-pathway-dependent manner. |
| format | Article |
| id | doaj-art-359acb2fa5884b8ab3c0ecf91018428d |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-359acb2fa5884b8ab3c0ecf91018428d2024-11-22T17:36:31ZengeLife Sciences Publications LtdeLife2050-084X2024-11-011310.7554/eLife.98716Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvaeFatima Tleiss0Martina Montanari1Romane Milleville2Olivier Pierre3Julien Royet4https://orcid.org/0000-0002-5671-4833Dani Osman5https://orcid.org/0000-0003-3880-3098Armel Gallet6https://orcid.org/0000-0002-2054-4780C Leopold Kurz7https://orcid.org/0000-0001-7081-3208Université Côte d'Azur, CNRS, INRAE, ISA, Nice, FranceAix-Marseille Université, CNRS, IBDM, Marseille, FranceAix-Marseille Université, CNRS, IBDM, Marseille, FranceUniversité Côte d'Azur, CNRS, INRAE, ISA, Nice, FranceAix-Marseille Université, CNRS, IBDM, Marseille, FranceUMR PIMIT (Processus Infectieux en Milieu Insulaire Tropical) CNRS 9192-INSERM 1187-IRD 249-Université de La Réunion, île de La Réunion, FranceUniversité Côte d'Azur, CNRS, INRAE, ISA, Nice, FranceAix-Marseille Université, CNRS, IBDM, Marseille, FranceMultiple gut antimicrobial mechanisms are coordinated in space and time to efficiently fight foodborne pathogens. In Drosophila melanogaster, production of reactive oxygen species (ROS) and antimicrobial peptides (AMPs) together with intestinal cell renewal play a key role in eliminating gut microbes. A complementary mechanism would be to isolate and treat pathogenic bacteria while allowing colonization by commensals. Using real-time imaging to follow the fate of ingested bacteria, we demonstrate that while commensal Lactiplantibacillus plantarum freely circulate within the intestinal lumen, pathogenic strains such as Erwinia carotovora or Bacillus thuringiensis, are blocked in the anterior midgut where they are rapidly eliminated by antimicrobial peptides. This sequestration of pathogenic bacteria in the anterior midgut requires the Duox enzyme in enterocytes, and both TrpA1 and Dh31 in enteroendocrine cells. Supplementing larval food with hCGRP, the human homolog of Dh31, is sufficient to block the bacteria, suggesting the existence of a conserved mechanism. While the immune deficiency (IMD) pathway is essential for eliminating the trapped bacteria, it is dispensable for the blockage. Genetic manipulations impairing bacterial compartmentalization result in abnormal colonization of posterior midgut regions by pathogenic bacteria. Despite a functional IMD pathway, this ectopic colonization leads to bacterial proliferation and larval death, demonstrating the critical role of bacteria anterior sequestration in larval defense. Our study reveals a temporal orchestration during which pathogenic bacteria, but not innocuous, are confined in the anterior part of the midgut in which they are eliminated in an IMD-pathway-dependent manner.https://elifesciences.org/articles/98716bacteriaimmunitypathogensintestineduoxtrpa1 |
| spellingShingle | Fatima Tleiss Martina Montanari Romane Milleville Olivier Pierre Julien Royet Dani Osman Armel Gallet C Leopold Kurz Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvae eLife bacteria immunity pathogens intestine duox trpa1 |
| title | Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvae |
| title_full | Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvae |
| title_fullStr | Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvae |
| title_full_unstemmed | Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvae |
| title_short | Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvae |
| title_sort | spatial and temporal coordination of duox trpa1 dh31 and imd pathways is required for the efficient elimination of pathogenic bacteria in the intestine of drosophila larvae |
| topic | bacteria immunity pathogens intestine duox trpa1 |
| url | https://elifesciences.org/articles/98716 |
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