Selective killing of Porphyromonas gingivalis by the membrane-active synthetic retinoid CD1530

This study aimed to evaluate the antibacterial activity of the synthetic retinoid CD1530 against Porphyromonas gingivalis and to elucidate its underlying antibacterial mechanism of action.

The antibacterial activity of CD1530 against P. gingivalis was determined by antimicrobial susceptibility testing. Bacterial morphological changes following CD1530 treatment were examined by microscopy. Membrane structural and functional integrity were assessed using fluorescence-based assays and flow cytometry. Tandem mass tag (TMT)-based quantitative proteomics and lipidomics were further employed to investigate the mechanisms underlying the antibacterial effects of CD1530.

CD1530 exhibited potent antibacterial activity against P. gingivalis. Mechanistic analyses revealed that CD1530 penetrated the outer membrane and disrupted the inner membrane of P. gingivalis. This membrane damage was associated with increased membrane fluidity, membrane depolarization, and potassium ion efflux, which were accompanied by metabolic disruption and bacterial cell death. Furthermore, the results indicated that differences in outer membrane permeability among Gram-negative bacteria species contributed to the selective antibacterial activity of CD1530.

CD1530 demonstrates potent antibacterial activity against P. gingivalis, primarily through disruption of bacterial membrane integrity and function. These findings suggest that CD1530 has potential as a membrane-active antibacterial agent for the treatment of P. gingivalis infections.

CD1530 selectively targets P. gingivalis via species-specific envelope properties, thereby supporting its potential as a narrow-spectrum therapeutic agent against this pathogen and possibly other susceptible Gram-negative bacteria.