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Recently, the interest is increasing to find alternatives to replace the usage of antibiotics since their massive and improper usage enhance the antibiotic resistance in human pathogens. In this study, for the first time we showed that the soil proteins have very high antibacterial activity (98% of growth inhibition) against methicillin resistant Staphylococcus aureus (MRSA), one of the most threatening human pathogens. We found that the protein extract (C3) from the forest with past intensive management showed higher antibacterial activity than that of unmanaged forest. The MIC and IC 50 were found to be 30 and 15.0 μg protein g−1 dry soil respectively. C3 was found to kill the bacteria by cell wall disruption and genotoxicity which was confirmed by optical and fluorescent microscopy and comet assay. According to qPCR study, the mecA (the antibiotic resistant gene) expression in MRSA was found to be down-regulated after C3 treatment. In contrast, C3 showed no hemolytic toxicity on human red blood cells which was confirmed by hemolytic assay. According to ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS), 144 proteins were identified in C3 among which the majority belonged to Gram negative bacteria (45.8%). Altogether, our results will help to develop novel, cost-effective, non-toxic and highly efficient antibacterial medicines from natural sources against antibiotic resistant infections. • Soil subjected to anthropogenic activities are hotspots for the pharmacological studies. • Soil proteins showed high antibacterial activity against MRSA. • They have multiple targets including bacterial cell wall and DNA. • Soil proteins are highly efficient, non-toxic and natural antibacterial compound. [ABSTRACT FROM AUTHOR]

Interactions of silver phosphate nanoparticles ( SPNPs) and selenium nanoparticles ( Se NPs) with Staphylococcus aureus cultures have been studied at the cellular, molecular and protein level. Significant antibacterial effects of both SPNPs and Se NPs on S. aureus were observed. At a concentration of 300 μM, SPNPs caused 37.5% inhibition of bacterial growth and Se NPs totally inhibited bacterial growth. As these effects might have been performed due to the interactions of nanoparticles with DNA and proteins, the interaction of SPNPs or Se NPs with the amplified zntR gene was studied. The presence of nanoparticles decreased the melting temperatures of the nanoparticle complexes with the zntR gene by 23% for Se NPs and by 12% for SPNPs in comparison with the control value. The concentration of bacterial metallothionein was 87% lower in bacteria after application of SPNPs (6.3 μg mg−1 protein) but was increased by 29% after addition of Se NPs (63 μg mg−1 protein) compared with the S. aureus control (49 μg mg−1 protein). Significant antimicrobial effects of the nanoparticles on bacterial growth and DNA integrity provide a promising approach to reducing the risk of bacterial infections that cannot be controlled by the usual antibiotic treatments. [ABSTRACT FROM AUTHOR]