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This study explores the impact of microbial dysbiosis and virulence factors on acne development. Through high-throughput 16S rRNA sequencing, we identified significant disruptions in the skin microbiome, particularly in comedones. Key virulence factors of <jats:italic>Cutibacterium acnes<\/jats:italic>, known as Christie\u2013Atkins\u2013Munch-Peterson (CAMP) factors, were assessed using both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models. Among these, CAMP2 and CAMP5 demonstrated the highest inflammatory and haemolytic activities in keratinocytes. Topical anti-IL-8 treatment in a murine model effectively reduced inflammation and suppressed CAMP expression. Structural analysis of CAMP3 uncovered distinct pathogenic features that, alongside CAMP5, were found to aggravate acne-like inflammation and sebaceous gland atrophy. 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