Aureimonas jatrophae sp. nov. and Aureimonas phyllosphaerae sp. nov., leaf-associated bacteria isolated from Jatropha curcas L. , originating from surface-sterilized leaf tissues of Jatropha curcas L. cultivars were characterized using a polyphasic taxonomic approach. Phylogenetic analyses based on 16S rRNA gene sequences indicated that all four isolates belong to the genus Aureimonas. In these analyses, strain L7-484 T appeared to be most closely related to Aureimonas ureilytica 5715S-12 T (95.7 % sequence identity). The 16S rRNA gene sequences of strains L7-456, L9-479 and L9-753 T were found to be identical and also shared the highest similarity with A. ureilytica 5715S-12 T (97.5 %). Both L7- 484T and L9-753 T contained Q-10 and Q-9 as predominant ubiquinones and diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, phosphatidyldimethylethanolamine, sulfoquinovosyldiacylglycerol and an aminophospholipid as the major polar lipids. C 18 : 1 v7c and C 16 : 0 were the major fatty acids. Similar to other species in the genus Aureimonas, hydroxylated fatty acids (e.g. C 18 : 1 2-OH) and cyclic fatty acids (C 19 : 0 cyclo v8c) were also present. The DNA G+C contents of L7-484 T and L9-753 T were 66.1 and 69.4 mol%, respectively. Strains L7-484 T and L9-753 T exhibited less than 40 % DNA-DNA hybridization both between themselves and to A. ureilytica KACC 11607

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In the process of investigating the antifungal structure-activity relationships (SAR) of borrelidin and discovering antifungal leads, a semisynthetic borrelidin analogue, BN-3b with antifungal activity against Candida albicans, was achieved. In this study, we found that oxidative damage induced by endogenous reactive oxygen species (ROS) plays an important role in the antifungal activity of BN-3b. Further investigation indicated that BN-3b stimulated ROS accumulation, increased malondialdehyde (MDA) levels, and decreased reduced/oxidized glutathione (GSH/GSSG) ratio. Moreover, BN-3b decreased mitochondrial membrane potential (MMP) and ATP generation. Ultrastructure analysis revealed that BN-3b severely damaged the cell membrane of C. albicans. Quantitative PCR (RT-qPCR) analysis revealed that virulence factors of C. albicans SAPs, PLB1, PLB2, HWP1, ALSs, and LIPs were all down-regulated after BN-3b exposure. We also found that BN-3b markedly inhibited the hyphal formation of C. albicans. In addition, in vivo studies revealed that BN-3b significantly prolonged survival and decreased fungal burden in mouse model of disseminated candidiasis.Candida albicans is an opportunistic fungal pathogen 1 , causing skin and mucosal infections in healthy individuals 2 . Moreover, C. albicans can cause fatal systemic disease when immune function is damaged 3 . Disseminated candidiasis caused by C. albicans is the main cause of death in immunocompromised patients 3,4 .Borrelidin (BN), an 18-membered macrolide polyketide 5 , was isolated from the fermentation broth of Streptomyces vinaceusdrappus 6 . In the process of investigating the antifungal SAR of BN and discovering antifungal leads, forty-seven borrelidin derivatives (BNs) were synthesized by our research group 5 . Among them, a BN ester analogue BN-3b was greatly promising antifungal candidate. The MIC (minimum inhibitory concentration) values of BN-3b against C. albicans and Candida parapsilosis were 50 μg/mL and 12.5 μg/mL, respectively (Table 1). In this study, we will explore the antifungal mechanism of BN-3b.Several studies have suggested that endogenous ROS mediated oxidative damage participate in the antifungal activity of amphotericin B (AMB) and fluconazole (FLC) 7-11 . These findings implied that oxidative stress involved in the antifungal mechanism of antifungal agents. ROS are the byproducts of cellular metabolism and mainly produced in the mitochondria 12 . However, overproduction of ROS resulted in damage of nucleic acids, proteins, and lipids 4 .C. albicans has developed an effective battery of virulence factors 13 that promote disease establishment and progression 14 . Among these virulence factors, lipases (LIPs), phospholipases, agglutinin-like sequences (ALSs), secreted aspartyl proteinases (SAPs), and hyphal wall protein (HWP1) are most significant in virulence [14][15][16][17] . Fungal virulence factors are potential targets for drug development 15 . In this study, we determined the expression of virulence factors (SAPs, PLB1, PLB2, HWP1, ALSs, and LIP...

Bafilomycin C1, which was isolated from Streptomyces albolongus in our previous work, exhibited strong cytotoxicity against several cancer cell lines. This study aimed to evaluate its antitumor effect on human hepatocellular cancer SMMC7721 cells and the underlying mechanism in vitro and in vivo. MTT assay revealed that bafilomycin C1 retarded SMMC7721 cell growth and proliferation. Western blot and real-time qPCR analysis revealed that bafilomycin C1 caused partial G0/G1 phase cell-cycle arrest, downregulated the expression of cyclin D3, cyclin E1, CDK2, CDK4, and CDK6 and upregulated the expression of p21. Moreover, bafilomycin C1 caused mitochondrial membrane dysfunction through oxidative stress. Furthermore, bafilomycin C1 decreased the expression of Bcl-2; increased the expression of Bax, p53, and P-p53; and increased cleavage of caspase-9 and caspase-3, thereby inducing the intrinsic caspase-dependent apoptotic pathway. In vivo experiments in mice suggested that bafilomycin C1 suppressed tumor growth with few side effects. Cell-cycle arrest and induced apoptosis in tumor tissues in a mouse model treated with bafilomycin C1 were demonstrated by histological analyses, western blot and TUNEL. These findings indicate that bafilomycin C1 may be a promising candidate for hepatic cellular cancer therapy.