Cutibacterium acnes inhibits Staphylococcus lugdunensis biofilm formation through inhibition of autolysis and purine biosynthesis.

Staphylococcus lugdunensis, while also a resident of the skin microbiota, is an opportunistic pathogen capable of causing severe infections, associated with its ability to form biofilms. Building on our previous observation that C. acnes secretes molecules capable of inhibiting S. lugdunensis biofilm formation without inhibiting planktonic growth, we investigated the underlying molecular mechanisms of this phenomenon.

Here, we demonstrate that cell-free supernatants from various C. acnes strains exhibit dose-dependent antibiofilm activity targeting the initial stages of S. lugdunensis biofilm development. Additionally, extracellular molecules from C. acnes cultures significantly reduced the ability of S. lugdunensis to adhere to and invade human epithelial cells (A549) and to adhere to keratinocytes (HaCaT). Transcriptomic analysis revealed that C. acnes-derived molecules significantly repressed the expression of genes involved in purine biosynthesis in S. lugdunensis, while inducing the expression of the negative regulators of autolysis, lrgA and lrgB.