Deciphering the Antibacterial Mode of Action of Alpha-Mangostin on RP62A Through an Integrated Transcriptomic and Proteomic Approach.

Alpha-mangostin (α-MG) is a natural xanthone reported to exhibit rapid bactericidal activity against Gram-positive bacteria, and may therefore have potential clinical application in healthcare sectors. This study sought to identify the impact of α-MG on RP62A through integrated advanced omic technologies. was challenged with sub-MIC (0.875 μg/ml) of α-MG at various time points and the differential expression pattern of genes/proteins were analyzed in the absence and presence of α-MG using RNA sequencing and LC-MS/MS experiments. Bioinformatic tools were used to categorize the biological processes, molecular functions and KEGG pathways of differentially expressed genes/proteins. qRT-PCR was employed to validate the results obtained from these analyses. Transcriptomic and proteomic profiling of α-MG treated cells indicated that genes/proteins affected by α-MG treatment were associated with diverse cellular functions. The greatest reduction in expression was observed in transcription of genes conferring cytoplasmic membrane integrity ( and ), cell division ( and ), teichoic acid biosynthesis ( and ), fatty-acid biosynthesis (, and ), biofilm formation () and DNA replication and repair machinery (, and ). Those with increased expression were involved in oxidative ( and ) and cellular stress response (, and ). The qRT-PCR analysis substantiated the results obtained from transcriptomic and proteomic profiling studies. Combining transcriptomic and proteomic methods provided comprehensive information about the antibacterial mode of action of α-MG. The obtained results suggest that α-MG targets through multifarious mechanisms, and especially prompts that loss of cytoplasmic membrane integrity leads to rapid onset of bactericidal activity.