Haobin Zhao

Biological activity of lipopeptides from Bacillus

The lipopeptides of Bacillus are small metabolites that contain a cyclic structure formed by 7–10 amino acids (including 2–4 d-amino acids) and a beta-hydroxy fatty acid with 13–19 C atoms. These lipopeptides exhibit a variety of biological activities, including interactions with biofilms, and anti-fungal, anti-inflammatory, anti-tumor, anti-virus, and anti-platelet properties. The multiple activities of lipopeptides have stimulated significant interest in the exploitation of these lipopeptides for use as antibiotics, feed additives, anti-tumor agents, urgent thrombolytic therapeutic agents, and drug delivery systems. Understanding the natural function of these structurally diverse lipopeptides in Bacillus provides insight into microbial regulatory programs and is required for efficient development of more effective products. Currently, there is still insufficient knowledge of the direct target of these lipopeptides, and continued efforts are needed to enhance their biosynthesis efficiency for industrial applications.

Cholesterol-Lowering Effects and Mechanisms in View of Bile Acid Pathway of Resveratrol and Resveratrol Glucuronides

Resveratrol (Res) was previously reported to be capable of lowering plasma TC and LDL-C. The mechanism behind Res is not clearly understood, although it is presumed to have an effect on bile acid metabolism in the liver: a significant way in eliminating cholesterol from the body. As one of the major metabolites of Res in the liver, resveratrol glucuronides (Gres) is suspected to also contribute to the overall cholestrol-lowering activity of Res, which needs to be studied. In this research, when HepG2 steatosis hepatic cells were treated with Res and Gres at different concentration levels, Res and Gres showed similar activity in lowering cellular TC content. The presence of Res and Gres caused a significant increase in hepatic CYP7A1 and BSEP, indicating the increase in the synthesis and efflux of bile acids, respectively. The reduction of HMG-CoAR tied to a decrease in de novo synthesis of cholesterol and the increase of ABCG5 suggested the increase of direct efflux of cholesterol. All above variations reduced the hepatic cholesterol level, which triggered the significant enhancement of LDLR, illustrating the improvement of clearance of LDL-C from the plasma and prevention of atherosclerosis. Overall, this study demonstrated both Res and Gres might have capabilities in lowering hepatic cholesterol through increasing in the synthesis and efflux of bile acids, and decreasing in synthesis and increasing in the efflux of cholesterol. Gres would have preferred potential than Res because of its lower cytotoxicity, which indicated that the action of the metabolites should also be considered in the future studies.

Potential of Bacillus subtilis lipopeptides in anti-cancer I: induction of apoptosis and paraptosis and inhibition of autophagy in K562 cells

The lipopeptide iturin from Bacillus subtilis has been found to have a potential inhibitory effect on breast cancer, alveolar adenocarcinoma, renal carcinoma, and colon adenocarcinoma. In this study, the potential of B. subtilis lipopeptides (a mixture of iturin homologues, concentration of 42.75%) to inhibit chronic myelogenous leukemia was evaluated using K562 myelogenous leukemia cells. The results showed that the lipopeptides could completely inhibit the growth of K562 at 100xa0μM, with an IC50 value of 65.76xa0μM. The lipopeptides inhibited the profile of K562 via three pathways: (1) induction of paraptosis indicated by the occurrence of cytoplasmic vacuoles, and swelling of the mitochondria and endoplasmic reticulum (ER) without membrane blebbing in the presence of a caspase inhibitor; (2) inhibition of autophagy progress illustrated by the upregulated expression of LCII and P62; and (3) induction of apoptosis by causing ROS burst, and induction of the intrinsic pathway indicated by the upregulated expression of cytochrome c (Cyto-c), bax, and bad, together with downregulated expression of Bcl-2. The ROS-dependent apoptosis and caspase-independent paraptosis were verified using the ROS inhibitor and caspase inhibitor, respectively. The extrinsic apoptosis pathway was not involved in the lipopeptide’s effects on K562. Overall, the B. subtilis lipopeptides (consisting of a majority of iturin) exhibited promising potential in inhibiting chronic myelogenous leukemia in vitro via simultaneously causing paraptosis, apoptosis, and inhibition of autophagy.

Lipopeptides from Bacillus subtilis have potential application in the winemaking process: inhibiting fungal and ochratoxin A contamination and enhancing esters and acids biosynthesis

Background and Aims n nAspergillus carbonarius is considered the major cause of ochratoxin A (OTA) contamination in grape products, especially wine. The lipopeptides produced by Bacillus subtilis have been found to inhibit A. carbonarius contamination and OTA production in grapes. In order to assess the potential application of these lipopeptides during the winemaking process, they were tested alone or in combination with SO2 to evaluate their effect on fungal growth and OTA contamination. nMethods and Results n nLipopeptides at 200 and 400 mg/L were added alone or in combination with SO2 during the winemaking process using naturally contaminated grapes. Aspergillus carbonarius was also manually inoculated before fermentation to simulate grapes with a high fungal contamination and to investigate the inhibitory effect of lipopeptides on OTA-producing fungi. The lipopeptides inhibited significantly fungal contamination and OTA production, much stronger than SO2 against OTA-producing A. carbonarius, at an optimum level of 200 mg/L. Yeast growth and biosynthesis of esters and acids were also promoted by lipopeptides during winemaking, which led to an improvement of wine flavour. nConclusions n nLipopeptides isolated from B. subtilis had a more potent inhibitory effect on fungal contamination and OTA accumulation than that of SO2 during winemaking. Moreover, lipopeptides had no negative effect on fermentation, wine composition and sensory attributes. nSignificance of the Study n nThese findings highlight the interesting possibility for the application of lipopeptides to replace or reduce the amount of SO2 added during winemaking, especially when the inhibition of fungal contamination and OTA accumulation is considered.

Mechanism and Anticancer Activity of the Metabolites of an Endophytic Fungi from Eucommia ulmoides Oliv

Backgroud: Pinoresinol (Pin) and pinoresinol monoglucoside (PMG) are plant-derived lignan molecules with multiple functions. We showed previously that an endophytic fungus from Eucommia ulmoides Oliv., Phomopsis sp. XP-8 is able to produce Pin and PMG.nnnOBJECTIVEnThis study was carried out to test the anti-tumor capability of the culture of XP-8 and identify the major effective compounds.nnnMETHODnThe fungal culture was added in the culture of HepG2 and K562 cells, and the viabilities of these cells were detected and the possible mechanism was analyzed.nnnRESULTnThe fungal culture showed significant capaiblity in decreasing the viability of tumor cells and induce apoptosis via up-regulation of the expression of apoptosis-related genes. It also significantly inhibited the adhesion and migration of HepG2 cells by blocking MMP-9 expression. Pin and PMG were isolated from the growth culture and shown to be the major effective components for inhibition.nnnCONCLUSIONnThe study indicated the potential application of XP-8 in the production of anti-tumour products by the bioconversion of glucose.

Iturin A-like lipopeptides from Bacillus subtilis trigger apoptosis, paraptosis, and autophagy in Caco-2 cells: ZHAO et al.

This study revealed that iturin A‐like lipopeptides produced by Bacillus subtillis induced both paraptosis and apoptosis in heterogeneous human epithelial colorectal adenocarcinoma (Caco‐2) cells. Autophagy was simultaneously induced in Caco‐2 cells treated with iturin A‐like lipopeptides at the early stage and inhibited at the later stage. A western blot analysis showed that the lipopeptides induced apoptosis in Caco‐2 cells via a mitochondrial‐dependent pathway, as indicated by upregulated expression of the apoptotic genes bax and bad and downregulated expression of the antiapoptotic gene bcl‐2. The induction of paraptosis in Caco‐2 cells was indicated by the occurrence of many cytoplasmic vacuoles accompanied by endoplasmic reticulum (ER) dilatation and mitochondrial swelling and dysfunction. ER stress also occurred with significant increases in reactive oxygen species and Ca2+ levels in cells. Autophagy was detected by a transmission electron microscopy analysis and by upregulated expression of LC3‐II and downregulated expression of LC3‐I. The inhibition of autophagy at the later stage was shown by upregulated expression of p62. This study revealed the capability of iturin A‐like B. subtilis lipopeptides to simultaneously execute antitumor potential via multiple pathways.

Origination, change, and modulation of geriatric disease-related gut microbiota during life

The age-related changes in the diversity and composition of the gut microbiota are well described in recent studies. These changes have been suggested to be influenced by age-associated weakening of the immune system and low-grade chronic inflammation, resulting in numerous age-associated pathological conditions. Gut microbiota homeostasis is important throughout the life of the host by providing vital functions to regulate various immunological functions and homeostasis. Based on published results, we summarize the relationship between the gut microbiota and aging-related diseases, especially Parkinson’s disease, immunosenescence, rheumatoid arthritis, bone loss, and metabolic syndrome. The change in composition of the gut microbiota and gut ecosystem during life and its influence on the host immunologic and metabolic phenotype are also analyzed to determine factors that affect aging-related diseases. Approaches to maintain host health and prevent or cure geriatric diseases are also discussed.

Production of bioproducts by endophytic fungi: chemical ecology, biotechnological applications, bottlenecks, and solutions

Endophytes are microorganisms that colonize the interior of host plants without causing apparent disease. They have been widely studied for their ability to modulate relationships between plants and biotic/abiotic stresses, often producing valuable secondary metabolites that can affect host physiology. Owing to the advantages of microbial fermentation over plant/cell cultivation and chemical synthesis, endophytic fungi have received significant attention as a mean for secondary metabolite production. This article summarizes currently reported results on plant-endophyte interaction hypotheses and highlights the biotechnological applications of endophytic fungi and their metabolites in agriculture, environment, biomedicine, energy, and biocatalysts. Current bottlenecks in industrial development and commercial applications as well as possible solutions are also discussed.