4.8 Article

Mining zebrafish microbiota reveals key community-level resistance against fish pathogen infection

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ISME JOURNAL
卷 15, 期 3, 页码 702-719

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DOI: 10.1038/s41396-020-00807-8

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资金

  1. Institut Pasteur
  2. French Government's Investissement d'Avenir program: Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' [ANR-10-LABX-62-IBEID]
  3. Fondation pour la Recherche Medicale [DEQ20180339185]
  4. EU-FP7 program
  5. Federation of European Biochemical Societies (FEBS)
  6. European Union [842629]
  7. Institut Carnot MS Postdoctoral fellowship
  8. Marie Curie Actions (MSCA) [842629] Funding Source: Marie Curie Actions (MSCA)

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This study identified a small consortium of culturable bacterial species that can protect zebrafish, as well as specific endogenous species and a bacterial assembly that contribute to community-level resistance against infection. The research demonstrates the importance of understanding the role of key endogenous bacteria in protecting hosts and the potential for engineering microbial communities for enhanced resilience against pathogens through direct experimental analysis.
The long-known resistance to pathogens provided by host-associated microbiota fostered the notion that adding protective bacteria could prevent or attenuate infection. However, the identification of endogenous or exogenous bacteria conferring such protection is often hindered by the complexity of host microbial communities. Here, we used zebrafish and the fish pathogenFlavobacterium columnareas a model system to study the determinants of microbiota-associated colonization resistance. We compared infection susceptibility in germ-free, conventional and reconventionalized larvae and showed that a consortium of 10 culturable bacterial species are sufficient to protect zebrafish. Whereas survival toF. columnareinfection does not rely on host innate immunity, we used antibiotic dysbiosis to alter zebrafish microbiota composition, leading to the identification of two different protection strategies. We first identified that the bacteriumChryseobacterium massiliaeindividually protects both larvae and adult zebrafish. We also showed that an assembly of 9 endogenous zebrafish species that do not otherwise protect individually confer a community-level resistance to infection. Our study therefore provides a rational approach to identify key endogenous protecting bacteria and promising candidates to engineer resilient microbial communities. It also shows how direct experimental analysis of colonization resistance in low-complexity in vivo models can reveal unsuspected ecological strategies at play in microbiota-based protection against pathogens.

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