The relationship between bacterial communities and their host is being extensively investigated for the potential to improve the host's health. Little is known about the interplay between the microbiota of parasites and the health of the infected host. Using nematode co-infection of lambs as a proof-of-concept model, the aim of this study was to characterise the microbiomes of nematodes and that of their host, enabling identification of candidate nematode-specific microbiota member(s) that could be exploited as drug development tools or for targeted therapy. Deep sequencing techniques were used to elucidate the microbiomes of different life stages of two parasitic nematodes of ruminants, Haemonchus contortus and Teladorsagia circumcincta, as well as that of the co-infected ovine hosts, pre- and post infection. Bioinformatic analyses demonstrated significant differences between the composition of the nematode and ovine microbiomes. The two nematode species also differed significantly. The data indicated a shift in the constitution of the larval nematode microbiome after exposure to the ovine microbiome, and in the ovine intestinal microbial community over time as a result of helminth co-infection. Several bacterial species were identified in nematodes that were absent from their surrounding abomasal environment, the most significant of which included Escherichia coli/Shigella. The ability to purposefully infect nematode species with engineered E. coli was demonstrated in vitro, validating the concept of using this bacterium as a nematode-specific drug development tool and/or drug delivery vehicle. To our knowledge, this is the first description of the concept of exploiting a parasite's microbiome for drug development and treatment purposes.
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http://dx.doi.org/10.1038/s41396-019-0462-4 | DOI Listing |
Zhonghua Xue Ye Xue Za Zhi
December 2024
Soochow Hopes Hematonosis Hospital, Suzhou 215128, China The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, Suzhou 215006, China.
This study aimed to compare the efficacy and safety between high-dose intravenous iron and oral iron in treating iron deficiency anemia (IDA) . This prospective randomized controlled study (1∶1) enrolled 338 patients with IDA at The First Affiliated Hospital of Soochow University, Suzhou Hongci Hematology Hospital, and Huai'an Second People's Hospital from June 1, 2022, to January 19, 2024. Of all the patients, 169 received high-dose intravenous iron therapy and 169 received oral iron treatment for 12 weeks of observation.
View Article and Find Full Text PDFMaturitas
December 2024
Division of Drug Informatics, Keio University Faculty of Pharmacy, Graduate School of Pharmaceutical Sciences, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. Electronic address:
Objectives: Factors affecting denosumab-induced hypocalcemia in male patients with osteoporosis remain unclear because of the small patient population. Nevertheless, it is important to explore male-specific risk factors. This study aimed to identify the factors affecting the development of denosumab-induced hypocalcemia in male patients with osteoporosis and compare them with those in female patients with osteoporosis.
View Article and Find Full Text PDFBiosens Bioelectron
December 2024
Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan. Electronic address:
We developed a novel DNA aptamer, D8#24S1, which specifically recognizes mertansine (DM1), the cytotoxic payload of the antibody-drug conjugate (ADC) trastuzumab emtansine (T-DM1), and applied it for T-DM1 analysis. D8#24S1 was obtained through SELEX and was shown to specifically recognize DM1 with high affinity (dissociation constant, K = 84.2 nM).
View Article and Find Full Text PDFJ Struct Biol
January 2025
Center of Structural Biology, Vanderbilt University, Nashville, TN, USA; Department of Chemistry, Vanderbilt University, Nashville, TN, USA; Institute for Drug Discovery, Institute for Computer Science, Wilhelm Ostwald Institute for Physical and Theoretical Chemistry, University Leipzig, Leipzig, Germany; Center for Scalable Data Analytics and Artificial Intelligence ScaDS.AI and School of Embedded Composite Artificial Intelligence SECAI, Dresden/Leipzig, Germany; Department of Pharmacology, Institute of Chemical Biology, Center for Applied Artificial Intelligence in Protein Dynamics, Vanderbilt University, Nashville, TN, USA. Electronic address:
High-throughput characterization of antibody-antigen complexes at the atomic level is critical for understanding antibody function enabling therapeutic development. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) enables rapid epitope mapping, but its data are too sparse for independent structure determination. In this study, we introduce RosettaHDX, a hybrid method that combines computational docking with differential HDX-MS data to enhance the accuracy of antibody-antigen complex models beyond what either method can achieve individually.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea. Electronic address:
Granulomas, dense clusters of immune cells and bacteria, are critical barriers in tuberculosis (TB) treatment. Recent advancements in TB management have highlighted granuloma control as a potential host-directed therapy (HDT) strategy. Although isoniazid (INH) is the first-line drug for TB therapy, its efficacy is limited to non-replicating Mycobacterium tuberculosis (Mtb) under granulomatous conditions, necessitating the development of more effective derivatives.
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