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Alexa Dinant,1 Ramiz A Boulos2,3 1AXD Pty Ltd, Semaphore Park, 2School of Chemical and Physical Sciences, Flinders University, Bedford Park, 3Boulos & Cooper Pharmaceuticals Pty Ltd, Port Adelaide, SA, Australia Background: Acne is a prominent skin condition affecting >80% of teenagers and young adults and ~650 million people globally. Isotretinoin, a vitamin A derivative, is currently the standard of care for treatment. However, it has a well-established teratogenic activity, a reason for the development of novel and low-risk treatment options for acne. Objective: To investigate the effectiveness of Zolav®, a novel antibiotic as a treatment for acne vulgaris. Materials and methods: Minimum inhibitory concentration of Zolav® against Propionibacterium acnes was determined by following a standard protocol using Mueller-Hinton broth and serial dilutions in a 96-well plate. Cytotoxicity effects on human umbilical vein endothelial cells and lung cells in the presence of Zolav® were investigated by determining the growth inhibition (GI50) concentration, total growth inhibition concentration, and the lethal concentration of 50% (LC50). The tryptophan auxotrophic mutant of Escherichia coli strain, WP2 uvrA (ATCC 49979), was used for the AMES assay with the addition of Zolav® tested for its ability to reverse the mutation and induce bacterial growth. The in vivo effectiveness of Zolav® was tested in a P. acnes mouse intradermal model where the skin at the infection site was removed, homogenized, and subjected to colony-forming unit (CFU) counts. Results: Susceptibility testing of Zolav® against P. acnes showed a minimum inhibitory concentration of 2 µg/mL against three strains with no cytotoxicity and no mutagenicity observed at the highest concentrations tested, 30 µM and 1,500 µg/plate, respectively. The use of Zolav® at a concentration of 50 µg/mL (q8h) elicited a two-log difference in CFU/g between the treatment group and the control. Conclusion: This study demonstrates the potential of Zolav® as a novel treatment for acne vulgaris. Keywords: acne, MscL, Zolav®, benzoyl peroxide, isotretinoin, antibiotic resistance