| Summary: | <i>Pseudomonas aeruginosa</i> is known to generate bacterial biofilms that increase antibiotic resistance. With the increase of multi-drug resistance in recent years, the formulation of a new therapeutic strategy has seemed urgent. Preliminary findings show that Prodigiosin (PG), derived from chromium-resistant <i>Serratia marcescens</i>, exhibited efficient anti-biofilm activity against <i>Staphylococcus aureus</i>. However, its anti-biofilm activity against <i>P. aeruginosa</i> remains largely unexplored. The anti-biofilm activity of PG against three clinical single drug-resistant <i>P. aeruginosa</i> was evaluated using crystal violet staining, and the viability of biofilms and planktonic cells were also assessed. A model of chronic lung infection was constructed to test the in vivo antibiofilm activity of PG. The results showed that PG inhibited biofilm formation and effectively inhibited the production of pyocyanin and extracellular polysaccharides in vitro, as well as moderated the expression of interleukins (IL-1β, IL-6, IL-10) and tumor necrosis factor (TNF-α) in vivo, which might be attributed to the downregulation of biofilm-related genes such as <i>algA</i>, <i>pelA</i>, and <i>pslM</i>. These findings suggest that PG could be a potential treatment for drug-resistant <i>P aeruginosa</i> and chronic biofilm infections.
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