<i>Sapindus mukorossi</i> as a Bioenhancer for the Biocidal Action of Polymyxin B

Bacterial infections remain a significant health concern, necessitating the continuous exploration of novel therapeutic strategies. <i>Sapindus mukorossi</i> extract, renowned for its bioactive saponins, presents a promising approach for combating bacterial pathogens. This study investigates the potential of <i>S. mukorossi</i> extract (SM) as a bioenhancer for the polymyxin B antibiotic (PMB) against four bacterial strains: <i>Staphylococcus aureus</i> (SA), <i>Staphylococcus epidermidis</i> (SE), <i>Pseudomonas aeruginosa</i> (PA), and <i>Escherichia coli</i> (EC). Research methods were used to determine the metabolic activity of the strains and the changes in their cell membrane permeability. Furthermore, advanced microscopic techniques (confocal and transmission electron microscopy) were used to confirm the viability and visualize morphological changes within selected strains. Obtained data were also correlated with the lipidomic and fatty acid methyl ester profiles of strains subjected to the described treatments. Results indicated that the conjugated treatment of bacterial cells with PMB and SM extract demonstrated an enhancement of bacterial total membrane permeability in comparison to the treatment with PMB alone. Notably, for the <i>S. aureus</i> strain, a significant decrease in viability was noted, which can be associated with the significant (in terms of statistical analysis) increase in cell membrane permeability for cells treated with SM and PMB, compared with samples treated with PMB alone. This was further conjoined and proven by the results of the FAME and lipidomic analyses. Specifically for <i>S. aureus</i>, an increase in branched fatty acids was detected in cells exposed to SM and SM + PMB. Additionally, the lipidomic analysis revealed notable membrane remodeling, characterized by an increase in lysyl-phosphatidylglycerol and diglucosyldiglyceride and a decrease in phosphatidylglycerol, in samples treated with SM and SM + PMB compared to the control group. This study underscores the potential of <i>S. mukorossi</i> extract as an enhancing agent to PMB in combination therapies against bacterial infections, paving the way for further investigations into its mechanistic insights and clinical applications.