Antibacterial activity and impact on keratinocyte cell growth of Cutibacterium acnes bacteriophages in a Cutibacterium acnes IA1- colonized keratinocyte model

Acne is an inflammatory disease in which microbial disbalance is represented by an augmented population of phylotype IA1 of Cutibacterium acnes. Various treatments for acne can cause side effects, and it has been reported that C. acnes is resistant to prescribed antibiotics. Phage therapy has been proposed as an alternative treatment for acne, given its species-specificity to kill bacteria, its relative innocuity, and its potential to manage antibioticresistant pathogens. Moreover, bacteriophages (phages) may modulate the microbiota and immune responses. Some studies have shown the potential use of phages in the treatment of acne. Nevertheless, the capacity to specifically reduce phylotype IA1 and the effect of phage treatment on skin cells are poorly understood. We assessed the capacity of phages to clear C. acnes IA1 and their effects on cell cytotoxicity and growth in HEKa cells- C. acnes IA1 co-culture. Phylotypes IA1 and IB had similar effects on HEKa cells, causing cytotoxicity and diminishing cell growth. Nevertheless, IA1 caused a higher impact on cell doubling time by increasing it 1.8 times more than cell growth control group. Even though there are no phages IA1-specific, we found phages that have a diminished effect on other phylotypes not related to acne. Phage treatment in general reduced IA1-caused cytotoxicity, with differences in efficacy among phages. In addition, phage purification was necessary to restore metabolic activity and growth of HEKa. Overall, phage evaluation as a therapeutic alternative should include phage-bacteria interactions and their impact on skin cells because of the differences that each phage can exhibit.