Adapting a phage to combat phage resistance

Elina Laanto, Kati Mäkelä, Ville Hoikkala, Janne Ravantti, Lotta-Riina Sundberg

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Phage therapy is becoming a widely recognized alternative for fighting pathogenic bacteria due to increasing antibiotic resistance problems. However, one of the common concerns related to the use of phages is the evolution of bacterial resistance against the phages, putatively disabling the treatment. Experimental adaptation of the phage (phage training) to infect a resistant host has been used to combat this problem. Yet, there is very little information on the trade-offs of phage infectivity and host range. Here we co-cultured a myophage FCV-1 with its host, the fish pathogenFlavobacterium columnare, in lake water and monitored the interaction for a one-month period. Phage resistance was detected within one day of co-culture in the majority of the bacterial isolates (16 out of the 18 co-evolved clones). The primary phage resistance mechanism suggests defense via surface modifications, as the phage numbers rose in the first two days of the experiment and remained stable thereafter. However, one bacterial isolate had acquired a spacer in its CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat)-Cas locus, indicating that also CRISPR-Cas defense was employed in the phage-host interactions. After a week of co-culture, a phage isolate was obtained that was able to infect 18 out of the 32 otherwise resistant clones isolated during the experiment. Phage genome sequencing revealed several mutations in two open reading frames (ORFs) likely to be involved in the regained infectivity of the evolved phage. Their location in the genome suggests that they encode tail genes. Characterization of this evolved phage, however, showed a direct cost for the ability to infect several otherwise resistant clones-adsorption was significantly lower than in the ancestral phage. This work describes a method for adapting the phage to overcome phage resistance in a fish pathogenic system.

Original languageEnglish
Article number291
JournalAntibiotics
Volume9
Issue number6
Number of pages11
ISSN2079-6382
DOIs
Publication statusPublished - 29 May 2020
MoE publication typeA1 Journal article-refereed

Bibliographical note

This article belongs to the Special Issue Phage Therapy: A biological Approach to Treatment of Bacterial Infections

Fields of Science

  • 1182 Biochemistry, cell and molecular biology
  • coevolution
  • fish pathogen
  • phage resistance
  • phage therapy
  • GLIDING MOTILITY
  • HOST-RANGE
  • ARMS-RACE
  • BACTERIOPHAGE
  • VIRULENCE
  • PRODUCTIVITY
  • EVOLUTION
  • PREDATION

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