Alleviation of arsenic-induced neurobehavioral defects with selenium in the larvae of Zaprionus indianus.

Selenium is an essential antioxidative micronutrient. This study was conducted to characterize the arsenic toxicity induced on the African fig fly, Zaprionus indianus, and its possible amelioration by selenium. We used computational tools and in vivo experiments to elucidate the mechanism of action of arsenic and selenium on Z. indianus larvae. We conducted experiments to study neurobehavioral parameters including learning and memory ability test and crawling and contraction assays. Our in silico study revealed twelve primary targets of arsenic trioxide. The gene ontology annotation of primary and secondary targets of arsenic trioxide revealed selenocysteine metabolic processes as one of the most reliable targets. To validate our in silico data, we analyzed the effect of arsenic trioxide on larvae of Z. indianus and tested the possible amelioration by sodium selenite supplementation. Our data demonstrated that the arsenic trioxide deteriorated the learning and memory ability of 2nd instar larvae of Z. indianus and such effect was reversed by sodium selenite supplementation. Furthermore, crawling and contraction assay done on 3rd instar larvae showed that there was reduction in both parameters upon arsenic trioxide exposure, which was restored with sodium selenite supplementation. Altogether, our computational and in vivo results strongly indicated that the neurobehavioral defects induced by arsenic trioxide on the larvae of Z. indianus can be successfully alleviated in the presence of sodium selenite.

Usnic acid modifies MRSA drug resistance through down-regulation of proteins involved in peptidoglycan and fatty acid biosynthesis.

Multidrug-resistant Staphylococcus aureus infections place a huge burden on the healthcare sector and the wider community. An increasing rate of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has necessitated the development of alternative agents. We previously reported that usnic acid (UA) has activity against MRSA; here, we report the effect of UA in combination with norfloxacin on the drug resistance of MRSA clinical isolates. We observed that the combination of UA-norfloxacin significantly reduces the bacterial burden in mouse models infected with S. aureus, without causing any detectable associated toxicity. Proteomic analysis indicated that UA-norfloxacin induces oxidative stress within cells, which leads to membrane damage and inhibits metabolic activity and biosynthesis of peptidoglycan and fatty acids. Collectively, this study provides evidence that UA in combination with norfloxacin may be a potential candidate for development into a resistance-modifying agent for the treatment of invasive MRSA infections.

Correction: Comprehensive Analysis of Temporal Alterations in Cellular Proteome of Bacillus subtilis under Curcumin Treatment.

[This corrects the article DOI: 10.1371/journal.pone.0120620.].

Comprehensive analysis of temporal alterations in cellular proteome of Bacillus subtilis under curcumin treatment.

Curcumin is a natural dietary compound with antimicrobial activity against various gram positive and negative bacteria. This study aims to investigate the proteome level alterations in Bacillus subtilis due to curcumin treatment and identification of its molecular/cellular targets to understand the mechanism of action. We have performed a comprehensive proteomic analysis of B. subtilis AH75 strain at different time intervals of curcumin treatment (20, 60 and 120 min after the drug exposure, three replicates) to compare the protein expression profiles using two complementary quantitative proteomic techniques, 2D-DIGE and iTRAQ. To the best of our knowledge, this is the first comprehensive longitudinal investigation describing the effect of curcumin treatment on B. subtilis proteome. The proteomics analysis revealed several interesting targets such UDP-N-acetylglucosamine 1-carboxyvinyltransferase 1, putative septation protein SpoVG and ATP-dependent Clp protease proteolytic subunit. Further, in silico pathway analysis using DAVID and KOBAS has revealed modulation of pathways related to the fatty acid metabolism and cell wall synthesis, which are crucial for cell viability. Our findings revealed that curcumin treatment lead to inhibition of the cell wall and fatty acid synthesis in addition to differential expression of many crucial proteins involved in modulation of bacterial metabolism. Findings obtained from proteomics analysis were further validated using 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) assay for respiratory activity, resazurin assay for metabolic activity and membrane integrity assay by potassium and inorganic phosphate leakage measurement. The gene expression analysis of selected cell wall biosynthesis enzymes has strengthened the proteomics findings and indicated the major effect of curcumin on cell division.