AUTHOR=Sivaranjani Murugesan , Leskinen Katarzyna , Aravindraja Chairmandurai , Saavalainen Päivi , Pandian Shunmugiah Karutha , Skurnik Mikael , Ravi Arumugam Veera 

TITLE=Deciphering the Antibacterial Mode of Action of Alpha-Mangostin on Staphylococcus epidermidis RP62A Through an Integrated Transcriptomic and Proteomic Approach

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00150

DOI=10.3389/fmicb.2019.00150

ISSN=1664-302X

ABSTRACT=<p><bold>Background:</bold> 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 <italic>Staphylococcus epidermidis</italic> RP62A through integrated advanced omic technologies.</p><p><bold>Methods:</bold><italic>S. epidermidis</italic> 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.</p><p><bold>Results:</bold> 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 (<italic>yidC2, secA</italic> and <italic>mscL</italic>), cell division (<italic>ftsY</italic> and <italic>divlB</italic>), teichoic acid biosynthesis (<italic>tagG</italic> and <italic>dltA</italic>), fatty-acid biosynthesis (<italic>accB, accC, fabD, fabH, fabI</italic>, and <italic>fabZ</italic>), biofilm formation (<italic>icaA</italic>) and DNA replication and repair machinery (<italic>polA, polC, dnaE</italic>, and <italic>uvrA</italic>). Those with increased expression were involved in oxidative (<italic>katA</italic> and <italic>sodA</italic>) and cellular stress response (<italic>clpB, clpC, groEL</italic>, and <italic>asp23</italic>). The qRT-PCR analysis substantiated the results obtained from transcriptomic and proteomic profiling studies.</p><p><bold>Conclusion:</bold> 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 <italic>S. epidermidis</italic> through multifarious mechanisms, and especially prompts that loss of cytoplasmic membrane integrity leads to rapid onset of bactericidal activity.</p>