A combination of ellagic acid and tetracycline inhibits biofilm formation and the associated virulence of <i>Propionibacterium acnes in vitro</i> and <i>in vivo</i>

<p><i>Propionibacterium acnes</i> is an opportunistic pathogen which has become notorious owing to its ability to form a recalcitrant biofilm and to develop drug resistance. The current study aimed to develop anti-biofilm treatments against clinical isolates of <i>P. acnes</i> under <i>in vitro</i> and <i>in vivo</i> conditions. A combination of ellagic acid and tetracycline (ETC; 250 μg ml⁻¹ + 0.312 μg ml⁻¹) was determined to effectively inhibit biofilm formation by <i>P. acnes</i> (80–91%) without affecting its growth, therefore potentially limiting the possibility of the bacterium attaining resistance. In addition, ETC reduced the production of extracellular polymeric substances (EPS) (20–26%), thereby making <i>P. acnes</i> more susceptible to the human immune system and antibiotics. The anti-biofilm potential of ETC was further substantiated under <i>in vivo</i> conditions using <i>Caenorhabditis elegans</i>. This study reports a novel anti-biofilm combination that could be developed as an ideal therapeutic agent with broad cosmeceutical and pharmaceutical applicability in the era of antibiotic resistance.</p