Antibacterial activity of the natural product elaiophylin against Streptococcus suis and its biofilm eradication effect

ABSTRACT The multidrug resistance (MDR) problem in Streptococcus suis ( S. suis ) is becoming increasingly severe, necessitating the development of novel antibacterial agents and strategies. In this study, seven elaiophylin derivatives were isolated from Streptomyces sp . WS-30248, and the antibacterial activity and mechanism of action of the principal compound, elaiophylin, against S. suis were systematically evaluated for the first time. Through comprehensive approaches including in vitro efficacy assays, biofilm inhibition and eradication tests, bacterial membrane integrity analysis, reactive oxygen species (ROS) level detection, and a mouse infection model, elaiophylin was found to exhibit significant antibacterial activity against multiple clinically MDR S. suis strains. Its minimum inhibitory concentration (MIC) was as low as 0.5 μg/mL, and complete bactericidal activity was achieved within 24 h at 4× MIC. The compound effectively inhibited and eradicated bacterial biofilms, directly killing embedded cells within the biofilm matrix. Mechanistic studies revealed that elaiophylin functions through multiple synergistic pathways, including disruption of bacterial membrane integrity and induction of massive ROS accumulation, thereby interfering with the proton motive force (PMF), depleting intracellular ATP, and blocking energy metabolism. In the mouse infection model, the elaiophylin-treated group showed a significantly increased survival rate of 60% and effectively reduced bacterial loads in tissues. This study demonstrates that elaiophylin is a highly promising natural candidate drug with multi-target synergistic effects, offering a new strategy to combat MDR S. suis and biofilm-associated infections. IMPORTANCE This study is the first to systematically elucidate the potent antibacterial activity and multi-mechanism synergistic action of elaiophylin against multidrug-resistant (MDR) Streptococcus suis . It exerts its effects through multiple targeted pathways, including disrupting membrane integrity and inducing ROS accumulation and can effectively eradicate biofilms. It provides a highly promising novel candidate drug and a new strategy to combat the increasingly severe problem of MDR S. suis infections, holding significant theoretical and clinical value.