Abstract

The emergence of drug resistant microbes over recent decades represents one of the greatest threats to human health; the resilience of many of these organisms can be attributed to their ability to produce biofilms. Natural products have played a crucial role in drug discovery, with microbial natural products in particular proving a rich and diverse source of antimicrobial agents. During antimicrobial activity screening, the strain Pseudomonas mosselii P33 was found to inhibit the growth of multiple pathogens. Following chemical investigation of this strain, pseudopyronines A-C were isolated as the main active principles, with all three pseudopyronines showing outstanding activity against Staphylococcus aureus. The analogue pseudopyronine C, which has not been well-characterized previously, displayed sub-micromolar activity against S. aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa. Moreover, the inhibitory abilities of the pseudopyronines against the biofilms of S. aureus were further studied. The results indicated all three pseudopyronines could directly reduce the growth of biofilm in both adhesion stage and maturation stage, displaying significant activity at micromolar concentrations.

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