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Antibacterial mode of action of alpha-mangostin on Staphylococcus epidermidis

ABSTRACT: Antibacterial mode of action of alpha-mangostin on Staphylococcus epidermidis

PROVIDER: PRJNA450895 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7027878_1.fastq.gz	Fastqsanger.gz
	SRR7027878_2.fastq.gz	Fastqsanger.gz

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Antibacterial mode of action of alpha-mangostin on Staphylococcus epidermidis

Project description: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 antibacterial mode of action of α-MG against Staphylococcus epidermidis RP62A through RNA-sequencing technology.

2018-04-19 | GSE113302 | GEO

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Project description:Lomitapide has been approved by FDA for years in reducing levels of low-density lipoprotein (LDL) in cases of familial hypercholesterolemia, whereas the antibacterial effect of lomitapide remains elusive. In this study, the inhibitory activities of lomitapide against Staphylococcus aureus, including both methicillin sensitive and resistant S. aureus, were first time discovered by drug repositioning. Lomitapide has shown the inhibitory activities not only on the planktonic cell growth but also on the biofilm formation of S. aureus. Moreover, lomitapide has shown mild bactericidal effect on planktonic cells of clinical S. aureus strains as indicated in time killing assay. In order to investigate the mechanism of actions of lomitapide, quantitative proteomics analysis was then applied and suggested that the pathways involved in the cell wall biosynthesis and protein biosynthesis might participate in its action mode, whereas the clinical applications of lomitapide antibacterial activities need to be extensive investigated.

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Project description:This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/The drug Praziquantel is the most commonly used drug for parasitic flatworms. It is currently being increasingly used in mass drug administration programmes, raising concerns over whether resistance will develop. Although widely used, its mode of action was until very recently uncertain. This study will investigate the praziquantel mode of action and resistance by sequencing the transcriptomes of Dugesia japonica and different stages and strains of S. mansoni.

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Project description:The resistance to antibiotics is an emerging problem, and necessitates novel antibacterial therapies. Cervimycins A–D are bi-glycosylated polyketides produced by Streptomyces tendae HKI 0179 with promising activity against Gram-positive bacteria. Microscopically, cervimycin C (CmC) treatment caused a spaghetti-like phenotype in Bacillus subtilis 168, with elongated curved cells, which stayed joined after cell division, and exhibited a chromosome segregation defect. Electron microscopy of cervimycin treated S. aureus revealed swelling of some cells, misshaped septa, and cell wall thickening and a rough cell wall surface. Incorporation tests in B. subtilis indicated an effect on DNA metabolism at high cervimycin-concentrations. Indeed, the down-regulation of the DNA gyrase subunit B (gyrB) acted synergistically with cervimycin, and the antibiotic inhibited the in vitro DNA gyrase supercoiling activity. To get a more global view on the mode of action of CmC, transcriptomics and proteomics of cervimycin treated versus untreated S. aureus cells were performed. Interestingly, and in contrast to the previous results, cervimycin did not induce the SOS response in S. aureus, which would indicate disturbance of the DNA gyrase. Instead, cervimycin induced the expression of the CtsR/HrcA heat shock operon and the expression of autolysins. Taken together, we identified the DNA gyrase as one target of cervimycin, but omics data revealed massive alterations in cervimycin treated S. aureus, involving cell wall modifying enzymes and protein stress response, indicating a complex mode of action of cervimycin, that is distinct from other antibiotics.

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

Project description:Background: Alpha-mangostin (?-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 ?-MG on Staphylococcus epidermidis RP62A through integrated advanced omic technologies. Methods: S. epidermidis was challenged with sub-MIC (0.875 ?g/ml) of ?-MG at various time points and the differential expression pattern of genes/proteins were analyzed in the absence and presence of ?-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 ?-MG treated cells indicated that genes/proteins affected by ?-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, fabI, 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 ?-MG. The obtained results suggest that ?-MG targets S. epidermidis through multifarious mechanisms, and especially prompts that loss of cytoplasmic membrane integrity leads to rapid onset of bactericidal activity.

| S-EPMC6372523 | biostudies-literature

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