4.6 Article

Individual bacteria in structured environments rely on phenotypic resistance to phage

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PLOS BIOLOGY
卷 19, 期 10, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.3001406

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资金

  1. Medical Research Council CASE PhD studentship [MR/P016162/1]
  2. Defence Science and Technology Laboratory
  3. Engineering and Physical Sciences Research Council through the CM-CDT [EP/L015110/1]
  4. Medical Research Council [MC_PC_17189]
  5. Gordon and Betty Moore Foundation Marine Microbiology Initiative [GBMF5514]
  6. European Research Council [773902-SuperPests, ERC-STG-2016-714478 -EVOIMMECH]
  7. Biotechnology and Biological Sciences Research Council [BB/T002522/1, BB/N017412/1]
  8. Natural Environment Research Council [NE/M018350/1, NE/R010935/1]
  9. Marie Sklodowska-Curie Actions fellowship [842646-PredProkDef]
  10. Engineering and Physical Sciences Research Council fellowship [EP/S001255/1]
  11. Royal Society [RG180007]
  12. NERC [NE/R010935/1] Funding Source: UKRI

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Bacteriophages offer a potential solution to antibiotic resistance, but genetic resistance remains a concern. In natural environments, evolution of bacterial resistance to phages is lower possibly due to spatial heterogeneity, with phenotypic resistance being a key determinant of survival in transient spatial refuges. Mathematical modelling suggests that the presence of spatial refuges leads to fundamentally different population dynamics in the bacterial response to phages.
Bacteriophages represent an avenue to overcome the current antibiotic resistance crisis, but evolution of genetic resistance to phages remains a concern. In vitro, bacteria evolve genetic resistance, preventing phage adsorption or degrading phage DNA. In natural environments, evolved resistance is lower possibly because the spatial heterogeneity within biofilms, microcolonies, or wall populations favours phenotypic survival to lytic phages. However, it is also possible that the persistence of genetically sensitive bacteria is due to less efficient phage amplification in natural environments, the existence of refuges where bacteria can hide, and a reduced spread of resistant genotypes. Here, we monitor the interactions between individual planktonic bacteria in isolation in ephemeral refuges and bacteriophage by tracking the survival of individual cells. We find that in these transient spatial refuges, phenotypic resistance due to reduced expression of the phage receptor is a key determinant of bacterial survival. This survival strategy is in contrast with the emergence of genetic resistance in the absence of ephemeral refuges in well-mixed environments. Predictions generated via a mathematical modelling framework to track bacterial response to phages reveal that the presence of spatial refuges leads to fundamentally different population dynamics that should be considered in order to predict and manipulate the evolutionary and ecological dynamics of bacteria-phage interactions in naturally structured environments.

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