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PreprintCited by 12Evolution and Genetic DynamicsBacterial Genetics and BiotechnologyGut microbiota and health

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Gut mélange à trois: fluctuating selection modulated by microbiota, host immune system, and antibiotics

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Barreto, Hugo C., Abreu, Beatriz, Gordo, Isabel·2021·Current Biology
DOI 10.1101/2021.12.30.474527

Preprint — published as 10.1016/j.cub.2022.06.017 · Paper page

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Abstract

SUMMARY: Iron is critical in host-microbe interactions, and its availability is tightly regulated in the mammalian gut. Antibiotics and inflammation can perturb iron availability in the gut, which could alter host-microbe interactions. Here, we show that an adaptive allele of iscR , a major regulator of iron homeostasis of Escherichia coli , is under fluctuating selection in the mouse gut. In vivo competitions in immune-competent, immune-compromised, and germ-free mice reveal that the selective pressure on an iscR mutant E. coli is modulated by the presence of antibiotics, the microbiota, and the immune system. In vitro assays show that iron availability is an important mediator of the iscR allele fitness benefits or costs. We identify Lipocalin-2, a host’s immune protein that prevents bacterial iron acquisition, as a major host mechanism underlying fluctuating selection of iscR . Our results provide a remarkable example of strong fluctuating selection acting on bacterial iron regulation in the mammalian gut.

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Metadata

Authors
Barreto, H. C., Abreu, B., & Gordo, I.
Affiliations
Instituto Gulbenkian de Ciência (PT)
Corresponding author
  • Barreto, Hugo C.
  • Gordo, Isabel
ORCID
Venue
Current Biology
Publisher
openRxiv
Published
2021-12-30
Volume
32
Issue
15
Pages
3261-3275.e4
ISSN
0960-9822 (ISSN-L)
DOI
10.1101/2021.12.30.474527
OpenAlex
W4284691909
Cited by
12
References
1
Citations by year
2026: 2 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 1
FWCI
1.51
Type
journal article
Language
en
Open access
Locations
  • Current Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Yakult Bio-Science Foundation
  • Fundação para a Ciência e a Tecnologia (0145-FEDER-022170, 01-0145, LISBOA‐01‐0145‐FEDER‐022170, PORTUGAL 2020, LISBOA-01-0145-FEDER- 016417, /2017, PD/BD/128429/2017, PTDC/BIA-EVL/7546/2020, LISBOA-01-0145-FEDER)
  • European Regional Development Fund (LISBOA-01-0145-FEDER- 016417, LISBOA-01-0145-FEDER-022170, 01-0145, PORTUGAL2020)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
fluctuating selection, iron homeostasis, IscR, Escherichia coli, gut microbiota, host-microbe interactions, neutrophil gelatinase-associated lipocalin, antibiotic effects on gut microbiota, immune system, germ-free mice, adaptive alleles, fitness costs and benefits
MeSH terms
Lipocalin-2, Animals, Anti-Bacterial Agents, Escherichia coli, Iron, Mammals, Transcription Factors, Gene Expression Regulation, Bacterial, Escherichia coli Proteins, Mice

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