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

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Sivaranjani , M , Leskinen , K , Aravindraja , C , Saavalainen , P , Pandian , S K , Skurnik , M & Ravi , A V 2019 , ' Deciphering the Antibacterial Mode of Action of Alpha-Mangostin on Staphylococcus epidermidis RP62A Through an Integrated Transcriptomic and Proteomic Approach ' , Frontiers in Microbiology , vol. 10 , 150 . https://doi.org/10.3389/fmicb.2019.00150

Titel: Deciphering the Antibacterial Mode of Action of Alpha-Mangostin on Staphylococcus epidermidis RP62A Through an Integrated Transcriptomic and Proteomic Approach
Författare: Sivaranjani, Murugesan; Leskinen, Katarzyna; Aravindraja, Chairmandurai; Saavalainen, Päivi; Pandian, Shunmugiah Karutha; Skurnik, Mikael; Ravi, Arumugam Veera
Upphovmannens organisation: Immunobiology Research Program
Department of Bacteriology and Immunology
Medicum
Research Programs Unit
University of Helsinki
Immunomics
Mikael Skurnik / Principal Investigator
Department of Diagnostics and Therapeutics
Clinicum
HUSLAB
Helsinki One Health (HOH)
Datum: 2019-02-06
Språk: eng
Sidantal: 16
Tillhör serie: Frontiers in Microbiology
ISSN: 1664-302X
DOI: https://doi.org/10.3389/fmicb.2019.00150
Permanenta länken (URI): http://hdl.handle.net/10138/300026
Abstrakt: Background: Alpha-mangostin (alpha-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 alpha-MG on Staphylococcus epidermidis RP62A through integrated advanced omic technologies. Methods: S. epidermidis was challenged with sub-MIC (0.875 mu g/ml) of alpha-MG at various time points and the differential expression pattern of genes/proteins were analyzed in the absence and presence of alpha-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. Results: Transcriptomic and proteomic profiling of alpha-MG treated cells indicated that genes/proteins affected by alpha-MG treatment were associated with diverse cellular functions. The greatest reduction in expression was observed in transcription of genes conferring cytoplasmic membrane integrity (yidC2, secA and mscL), cell division (ftsY and divlB), teichoic acid biosynthesis (tagG and dltA), fatty-acid biosynthesis (accB, accC, fabD, fabH, fabl, and fabZ), biofilm formation (icaA) and DNA replication and repair machinery (polA, polC, dnaE, and uvrA). Those with increased expression were involved in oxidative (katA and sodA) and cellular stress response (clpB, clpC, groEL, and asp23). The qRT-PCR analysis substantiated the results obtained from transcriptomic and proteomic profiling studies. Conclusion: Combining transcriptomic and proteomic methods provided comprehensive information about the antibacterial mode of action of alpha-MG. The obtained results suggest that alpha-MG targets S. epidermidis through multifarious mechanisms, and especially prompts that loss of cytoplasmic membrane integrity leads to rapid onset of bactericidal activity.
Subject: RNA-sequencing
LC-MS/MS
bactericidal
alpha-mangostin
cytoplasmic membrane
XANTHONE DERIVATIVES
BACILLUS-SUBTILIS
ANTIMICROBIALS
DISCOVERY
PLANT
RESISTANCE
VANCOMYCIN
INHIBITOR
RELEVANCE
BIOFILMS
3111 Biomedicine
1183 Plant biology, microbiology, virology
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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