A1 Journal article (refereed)
Bacteriophage Resistance Affects Flavobacterium columnare Virulence Partly via Mutations in Genes Related to Gliding Motility and Type IX Secretion System (2021)

Kunttu, H. M. T., Runtuvuori-Salmela, A., Sundell, K., Wiklund, T., Middelboe, M., Landor, L., Ashrafi, R., Hoikkala, V., & Sundberg, L.-R. (2021). Bacteriophage Resistance Affects Flavobacterium columnare Virulence Partly via Mutations in Genes Related to Gliding Motility and Type IX Secretion System. Applied and Environmental Microbiology, 87(16), e00812-21. https://doi.org/10.1128/AEM.00812-21

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Publication details

All authors or editors: Kunttu, Heidi M. T.; Runtuvuori-Salmela, Anniina; Sundell, Krister; Wiklund, Tom; Middelboe, Mathias; Landor, Lotta; Ashrafi, Roghaieh; Hoikkala, Ville; Sundberg, Lotta-Riina

Journal or series: Applied and Environmental Microbiology

ISSN: 0099-2240

eISSN: 1098-5336

Publication year: 2021

Volume: 87

Issue number: 16

Pages range: e00812-21

Publisher: American Society for Microbiology

Publication country: United States

Publication language: English

DOI: https://doi.org/10.1128/AEM.00812-21

Publication open access: Not open

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Web address of parallel published publication (pre-print): https://www.biorxiv.org/content/10.1101/2020.10.02.323337v2

Abstract

Increasing problems with antibiotic resistance has directed interest towards phage therapy in the aquaculture industry. However, phage resistance evolving in target bacteria is considered a challenge. To investigate how phage resistance influences the fish pathogen Flavobacterium columnare, two wild-type bacterial isolates, FCO-F2 and FCO-F9, were exposed to phages (FCO-F2 to FCOV-F2, FCOV-F5 and FCOV-F25, and FCO-F9 to FCL-2, FCOV-F13 and FCOV-F45), and resulting phenotypic and genetic changes in bacteria were analyzed. Bacterial viability first decreased in the exposure cultures, but started to increase after 1-2 days, along with a change in colony morphology from original rhizoid to rough, leading to 98% prevalence of the rough morphotype. Twenty-four isolates (including four isolates from no-phage treatments) were further characterized for phage resistance, antibiotic susceptibility, motility, adhesion and biofilm formation, protease activity, whole genome sequencing and virulence in rainbow trout fry. The rough isolates arising in phage exposure were phage-resistant with low virulence, whereas rhizoid isolates maintained phage susceptibility and high virulence. Gliding motility and protease activity were also related to the phage susceptibility. Observed mutations in phage-resistant isolates were mostly located in genes coding for type IX secretion system, a component of the Bacteroidetes gliding motility machinery. However, not all phage-resistant isolates had mutations, indicating that phage resistance in F. columnare is a multifactorial process including both genetic mutations and changes in gene expression. Phage resistance may not, however, be a challenge for development of phage therapy against F. columnare infections, since phage resistance is associated with decrease in bacterial virulence.

Keywords: bacteria; bacteriophages; phage therapy; resistance (medicine); virulence; mutations; fish diseases

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