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Abstract

uses multiple type VI secretion systems (T6SSs) to manipulate eukaryotic cells, kill competing microbes and take up nutrients. Bacterial strains are known to differ in their T6SS apparatus and the toxic effector proteins responsible for killing. The ability to eliminate competitors has been repeatedly demonstrated in lab studies, but much less is known about effector genotypes during infection. We used comparative genomics to test for the presence and absence of T6SS effector genes in over 450 clinical isolates from people with cystic fibrosis in Copenhagen (Denmark) and complemented these findings with data of 52 isolates from people with cystic fibrosis in London (UK). We found natural variation in the occurrence and combination of effector genes. Patients were typically infected with isolates that differ in their effector gene sets but show no statistically significant association between the number of effector genes and chronic infection. Isolates with a pair of T6SS effector and immunity genes and isolates without these genes, which would be expected to kill each other based on existing work in the laboratory, were found on the same individual. Taking the isolates’ phylogeny and sampling times into account, we identified five putative loss events of effector genes during infection. Although the impact of our findings for infected individuals will require further investigation, we demonstrate the extent of strain-level variation in T6SS effector genes in clinical isolates.

Funding
This study was supported by the:
  • European Research Council (Award CoG 647586)
    • Principal Award Recipient: AshleighS. Griffin
  • Novo Nordisk Foundation (Award NNF19OC0056411)
    • Principal Award Recipient: HelleKrogh Johansen
  • European Molecular Biology Organization (Award ALTF 80-2015)
    • Principal Award Recipient: DanielUnterweger
  • Daimler und Benz Stiftung (Award 32-10/18)
    • Principal Award Recipient: DanielUnterweger
  • German Cystic Fibrosis Association
    • Principal Award Recipient: DanielUnterweger
  • Deutsche Forschungsgemeinschaft (Award CRC1182)
    • Principal Award Recipient: DanielUnterweger
  • Deutsche Forschungsgemeinschaft (Award EXC2167)
    • Principal Award Recipient: DanielUnterweger
  • Deutsche Forschungsgemeinschaft (Award RU5042)
    • Principal Award Recipient: DanielUnterweger
  • Bundesministerium für Bildung und Forschung (Award 01KI2020)
    • Principal Award Recipient: DanielUnterweger
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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/content/journal/mgen/10.1099/mgen.0.001555
2025-11-07
2025-12-16

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