A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Adapting a Phage to Combat Phage Resistance (2020)


Laanto, Elina; Mäkelä, Kati; Hoikkala, Ville; Ravantti, Janne J.; Sundberg, Lotta-Riina (2020). Adapting a Phage to Combat Phage Resistance. Antibiotics, 9 (6), 291. DOI: 10.3390/antibiotics9060291


JYU-tekijät tai -toimittajat


Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: Laanto, Elina; Mäkelä, Kati; Hoikkala, Ville; Ravantti, Janne J.; Sundberg, Lotta-Riina

Lehti tai sarja: Antibiotics

eISSN: 2079-6382

Julkaisuvuosi: 2020

Volyymi: 9

Lehden numero: 6

Artikkelinumero: 291

Kustantaja: MDPI

Julkaisumaa: Sveitsi

Julkaisun kieli: englanti

DOI: http://doi.org/10.3390/antibiotics9060291

Avoin saatavuus: Open access -julkaisukanavassa ilmestynyt julkaisu

Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/69724


Tiivistelmä

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 pathogen Flavobacterium 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.


YSO-asiasanat: bakteriofagit; fagiterapia; kalataudit; lääkeresistenssi; evoluutio

Vapaat asiasanat: coevolution; fish pathogen; phage resistance; phage therapy


Liittyvät organisaatiot


Hankkeet, joissa julkaisu on tehty


OKM-raportointi: Kyllä

Raportointivuosi: 2020


Viimeisin päivitys 2020-18-08 klo 13:43