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.
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.
Project description:S. aureus and S. epidermidis were challenged with D-sphingosine, an antimicrobial lipid similar to sphingosines found in the major staphylococcal niche- human skin. Comparison of responses was used to identify resistance mechanisms and likely mode of action
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.
Project description:In the present study, we investigated albofungin’s antibacterial, biofilm inhibition, and eradication activity as well as its potential mode of action against drug-resistant Vibrio parahaemolyticus.
Project description:This SuperSeries is composed of the following subset Series: GSE21008: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: atrazine GSE21010: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: cadmium GSE21011: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: fluoranthene Refer to individual Series
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.
Project description:Infections associated with antimicrobial-resistant bacteria now represent a significant threat to human health using conventional therapy, necessitating the development of alternate and more effective antibacterial compounds. Silver nanoparticles (Ag NPs) have been proposed as potential antimicrobial agents to combat infections. A complete understanding of their antimicrobial activity is required before these molecules can be used in therapy. Lysozyme coated Ag NPs were synthesized and characterized by TEMEDS, XRD, UV-vis, FTIR spectroscopy, zeta potential, and oxidative potential assay. Biochemical assays and deep level transcriptional analysis using RNA sequencing were used to decipher how Ag NPs exert their antibacterial action against multi-drug resistant Klebsiella pneumoniae MGH78578. RNAseq data revealed that Ag NPs induced a triclosan-like bactericidal mechanism responsible for the inhibition of the type II fatty acid biosynthesis. Additionally, released AgC generated oxidative stress both extra and intracellularly in K. pneumoniae. The data showed that triclosan-like activity and oxidative stress cumulatively underpinned the antibacterial activity of Ag NPs. This result was confirmed by the analysis of the bactericidal effect of Ag NPs against the isogenic K. pneumoniae MGH78578 1soxS mutant, which exhibits a compromised oxidative stress response compared to the wild type. Silver nanoparticles induce a triclosan like antibacterial action mechanism in multi-drug resistant K. pneumoniae. This study extends our understanding of anti-Klebsiella mechanisms associated with exposure to Ag NPs. This allowed us to model how bacteria might develop resistance against silver nanoparticles, should the latter be used in therapy.