1887

Abstract

is a critical priority pathogen for novel antimicrobials (World Health Organization) because of the rise in nosocomial infections and its ability to evolve resistance to last resort antibiotics. is thus a priority target for phage therapeutics. Two strains of a novel, virulent bacteriophage (LemonAid and Tonic) able to infect carbapenem-resistant (strain NCTC 13420), were isolated from environmental water samples collected through a citizen science programme.

Phage-host coevolution can lead to emergence of host resistance, with a concomitant reduction in the virulence of host bacteria; a potential benefit to phage therapy applications.

and assays, genomics and microscopy techniques were used to characterize the phages; determine mechanisms and impact of phage resistance on host virulence, and the efficacy of the phages against .

developed resistance to both viruses, LemonAid and Tonic. Resistance came at a cost to virulence, with the resistant variants causing significantly reduced mortality in a larval model. A replicated 8 bp insertion increased in frequency (~40 % higher frequency than in the wild-type) within phage-resistant mutants, putatively resulting in early truncation of a protein of unknown function. Evidence from comparative genomics and an adsorption assay suggests this protein acts as a novel phage receptor site in . We find no evidence linking resistance to changes in capsule structure, a known virulence factor. LemonAid efficiently suppressed growth of across a wide range of titres. However, , while survival of infected larvae significantly increased with both remedial and prophylactic treatment with LemonAid (10 p.f.u. ml), the effect was weak and not sufficient to save larvae from morbidity and mortality.

While LemonAid and Tonic did not prove effective as a treatment in a larvae model, there is potential to harness their ability to attenuate virulence in drug-resistant .

Funding
This study was supported by the:
  • Wellcome (Award 218247/Z/19/Z)
    • Principle Award Recipient: BenTemperton
  • Medical Research Council
    • Principle Award Recipient: BenTemperton
  • GW4 BIOMED MRC DTP (Award MR/W006308/1)
    • Principle Award Recipient: BenTemperton
  • 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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2024-05-14
2024-05-23
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