Evolution of virulence in Klebsiella pneumoniae treated with phage cocktails
(English)Manuscript (preprint) (Other academic)
The worldwide emergence and spread of multidrug-resistant bacteria is a major concern in modern medicine, and threatens the once established control over bacterial infections. Phage therapy has been suggested as one potential solution to the problem of finding new antibacterial agents. Bacteria are known to evolve resistance against bacteriophages but in many cases phage-resistance comes with a cost on bacterial virulence in multicellular hosts. We investigated how the virulence of a clinical isolate of K. pneumoniae Kpn524 evolves in response to exposure to phage cocktails in the phage-resistant bacteria that would potentially survive the phage treatment. We found that the exposure to multiple phages was linked to lowered virulence in the phage-resistant bacteria, when measured in vivo with Galleria mellonella. However, two phages were found to increase the bacterial virulence when they were administered on the bacteria individually, and this was associated with an increased growth rate. Across all treatments, biofilm production was negatively correlated with virulence, whereas growth rate had a positive correlation with bacterial virulence. Our findings suggest that bacterial virulence is attenuated in the presence of multiple phages, possibly due to a trade-off between phage resistance andrate of replication. However, this is dependent on the composition of the phage cocktail.This is the first study to report increased bacterial virulence associated with exposure tolytic bacteriophages and our results call for meticulous consideration when choosingphages for phage cocktails, as phages with certain identity could have detrimentally adverse effects on the success of the treatment.
Evolutionary Biology Genetics Microbiology
Research subject Molecular Genetics
IdentifiersURN: urn:nbn:se:su:diva-115902OAI: oai:DiVA.org:su-115902DiVA: diva2:800967