Copper Homeostasis in Aspergillus fumigatus: Opportunities for Therapeutic Development

Conclusions Because the expression of copper tolerance genes is critical for the survival and virulence of fungal pathogens, pharmacological disruption of the function of copper tolerance genes would be predicted to have the following beneficial effects: (1) Induce fungal death: the loss of copper tolerance genes would lead to toxic levels of copper that would be expected to have fungistatic and/or fungicidal effects on the organism. (2) Enhance the activity of current antifungal drugs: the clinical efficacy of current antifungal drugs may be compromised by intrinsic or acquired resistance. Combination antifungal therapy with agents of different mechanistic classes could promote fungal killing and clinical efficacy and provide an alternative to monotherapy regimens. This suggests that combining inhibitors of copper tolerance proteins with one or more current antifungals could increase efficacy, promote fungal killing, and prevent the emergence of drug resistance more effectively than monotherapy regimens. In particular, combination therapy might reduce the hepatotoxicity caused by long-term exposure to high doses of azoles drugs. Thus, the AfAceA and crpA copper tolerance genes may be potential drug targets, although deletion of these genes in A. fumigatus leads only to attenuated virulence, not avirulence. Taken together, the regulation of copper homeostasis provides promising therapeutic targets for combating A. fumigatus infection. Furthermore, by targeting copper homeost...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research

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J. Mater. Chem. A, 2019, Accepted Manuscript DOI: 10.1039/C9TA08603J, CommunicationFangwei Peng, Lei Yu, Pengyue Gao, Xiaozhen Liao, Jianguo Wen, Yushi He, Guoqiang Tan, Yang Ren, Zi-Feng Ma The microstructure and morphology of the crystal play an important role in physical and electrochemical properties of the electrode materials. Here we report a highly crystalline microcube structure of Na-rich... The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - J. Mater. Chem. latest articles - Category: Chemistry Authors: Source Type: research
We report 15 new Cu(II) complexes with tridentate NNO -acylenamino ligands derived from 2-picolylamine and bearing up to three alkyl, alkoxy, alkoxycarbonyl, or (pseudo)halide substituents. The structures of nine complexes... The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - Dalton Trans. latest articles - Category: Chemistry Authors: Source Type: research
ConclusionThe traditional Chinese version of the ETDQ-7 is a valid and reliable, disease-specific rating scale that can be used to quantitatively evaluate the severity of subjective symptoms of ETD in adult patients.
Source: Journal of the Formosan Medical Association - Category: General Medicine Source Type: research
Publication date: Available online 17 September 2019Source: Microbial PathogenesisAuthor(s): Pingping Jiang, Wentao Yang, Yubei Jin, Haibin Huang, Chunwei Shi, Yanlong Jiang, Jianzhong Wang, Yuanhuan Kang, Guilian Yang, Chunfeng WangAbstractLactobacillus reuteri, a typical intestinal symbiotic bacterium, plays an important role in maintaining intestinal flora stability and host health. However, the effect of Lactobacillus reuteri on peritoneal macrophages has not been thoroughly studied. Our study indicated that Lactobacillus reuteri could activate macrophages and that macrophages treated with Lactobacillus reuteri have an...
Source: Microbial Pathogenesis - Category: Infectious Diseases Source Type: research
Source: Patient Preference and Adherence - Category: International Medicine & Public Health Tags: Patient Preference and Adherence Source Type: research
In this study, a specific and sensitive LC-MS/MS method has been developed and validated, for the quantification of ilaprazole enantiomers in the rat plasma, using R-lansoprazole as the internal standard. The enantioseparation was achieved on a CHIRALPAK AS-RH column (4.6 mm × 150 mm, i.d. 5 μm), with a mobile phase composed of 10 mM ammonium acetate aqueous solution and acetonitrile (60:40, v/v), at a flow-rate of 0.5 mL/min. The method was validated over the concentration range of 0.5–300 ng/mL for both, R- and S -ilaprazole. The lower limit of quantification was 0.5 ng/mL for both enanti...
Source: Journal of Pharmaceutical Analysis - Category: Drugs & Pharmacology Source Type: research
ConclusionsOur data show that KLHTT has anti-neutrophilic inflammatory effects in inhibiting ROS generation and cell adhesion. KLHTT also mitigated NET formation, mainly via an ROS-dependent pathway. In addition, KLHTT reduced neutrophil infiltration and improved the severity of IMQ-induced psoriasis-like skin inflammation in mice. Therefore, KLHTT may prove to be a safe and effective psoriasis therapy in the future.Graphical abstract
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 18 September 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Allan Artavia-León, Miguel Pacheco-Leiva, Cristofer Moya-Román, Natalia Rodríguez-Hernández, Adrián A. Pinto-TomásAnts have been widely studied, with 14,000 described species, but it is not until recently that they gained attention as sources for antimicrobial drug discovery. An increasing amount of studies are investigating ant-microbe symbioses, and clear benefits from their microbial counterparts have been experimentally demonstrated for ants in the tribes Attini, Camponoti...
Source: Drug Discovery Today: Disease Models - Category: Drugs & Pharmacology Source Type: research
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Source: Advances in Skin and Wound Care - Category: Dermatology Tags: ONLINE EXCLUSIVE Source Type: research
Sclerocarya birrea (Sb), Psidium guajava (Pg) and Eucalyptus camaldulensis (Ec) are widely used in traditional medicine for the treatment of many diseases, some of which were related to oxidative stress and parasitic diseases. Their essential oils (EO) were analyzed by GC/MS and FID and tested in vitro for their antioxidant activities (DPPH), their anti-trypanosomal and anti-plasmodial activ...
Source: Journal of Medicinal Plants Research - Category: Complementary Medicine Source Type: research
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