Article
Pharmacology & Pharmacy
Arnau Biosca, Miriam Ramirez, Alex Gomez-Gomez, Aritz Lafuente, Valentin Iglesias, Oscar J. Pozo, Santiago Imperial, Xavier Fernandez-Busquets
Summary: Resistance of the malaria parasite to artemisinin calls for the identification of new fast-acting antimalarials. In this study, the compound domiphen bromide (DB) is characterized as a rapid inhibitor of the malaria parasite, potentially useful for future antimalarial treatments.
Article
Nutrition & Dietetics
Semira R. Ortiz, Alexander Heinz, Karsten Hiller, Martha S. Field
Summary: Erythritol synthesis in human lung carcinoma cells is proportional to flux through the pentose phosphate pathway (PPP) and regulated by non-oxidative PPP enzymes.
FRONTIERS IN NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Mubarak A. Alamri, Sajjad Ahmad, Safar M. Alqahtani, Muhammad Irfan, Alhumaidi B. Alabbas, Muhammad Tahir Ul Qamar
Summary: Tuberculosis remains a major global public health concern. The development of new drugs is necessary due to the emergence of drug-resistant strains of Mycobacterium tuberculosis. In this study, comprehensive computational methods were used to identify compounds that bind to essential enzymes involved in biotin synthesis and ligation of M. tuberculosis. Two compounds were found to consistently bind to the enzymes with high affinity. These compounds could potentially be used in the design of effective anti-tuberculosis therapeutics by inhibiting bacterial growth through blocking biotin biosynthesis.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Materials Science, Multidisciplinary
Teliang Lu, Xinyuan Yuan, Luhui Zhang, Fupo He, Xiaolan Wang, Yu Zhang, Jiandong Ye
Summary: By introducing a high throughput experimental/screening method into elements-doped calcium phosphate, this study successfully synthesized zinc-doped BCP with gradient doping content and investigated the effects of doping content on its properties. The results showed that proper zinc doping could promote osteogenic differentiation of bone marrow mesenchymal stem cells, but high doping content may lead to cell apoptosis.
APPLIED MATERIALS TODAY
(2021)
Article
Multidisciplinary Sciences
Saima Bashir, Sandra Kik, Morten Ruhwald, Amir Khan, Muhammad Tariq, Hamidah Hussain, Claudia M. Denkinger
Summary: This study analyzed the cost of implementing computer-aided detection (CAD) software for detecting tuberculosis (TB) from chest X-ray images. The findings suggest that using CAD software could enable large-scale screening programs in high TB-burden countries and be less costly than relying solely on radiologists.
Article
Biotechnology & Applied Microbiology
Hyun Gyu Hwang, Myung Hyun Noh, Mattheos A. G. Koffas, Sungho Jang, Gyoo Yeol Jung
Summary: Recombinant microbes provide a promising alternative for producing naringenin, a key molecular scaffold for flavonoids. In this study, a systematic strategy for multi-level optimization of biosynthetic pathways was introduced, resulting in a significant increase in naringenin production. Through the construction of a combinatorial library covering both transcription and translation stages, improved strains were identified, leading to a 3-fold increase in naringenin production compared to traditional methods.
METABOLIC ENGINEERING
(2021)
Article
Microbiology
Nupur Angrish, Neha Lalwani, Garima Khare
Summary: Tuberculosis is a devastating infectious disease, and the emergence of drug-resistant strains has made treatment challenging. This study investigates the possibility of targeting the enzyme DapB to develop new anti-TB drugs and demonstrates the importance of DapB in the growth of M. tb.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Stephanie Henkel, Nora Frohnecke, Deborah Maus, Malcolm J. McConville, Michael Laue, Martin Blume, Frank Seeber
Summary: A study found that knocking down the ferredoxin protein in the parasite Toxoplasma gondii leads to impaired cellular metabolism, inhibited parasite growth, and eventually parasite death. This phenotype is not associated with changes in the apicoplast or overall cell morphology, but is related to a significant decrease in the levels of isoprenoid metabolites and impaired cellular motility. The findings suggest that ferredoxin could be a potential drug target for apicomplexan parasites.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biophysics
Fei Yan, Shengui He, Xiuyan Han, Jiayue Wang, Xiangge Tian, Chao Wang, Tony D. James, Jingnan Cui, Xiaochi Ma, Lei Feng
Summary: Tuberculosis is a major threat to public health globally. The usage of β-lactam antibiotics in treating TB is limited due to the presence of β-lactamase in Mycobacterium tuberculosis, which causes antibiotic resistance. However, combining β-lactam antibiotics with a β-lactamase inhibitor can overcome this resistance. In this study, a near-infrared fluorescent probe LXMB was developed for real-time detection and imaging of Blac activity in Mtb. A high-throughput screening platform was established using LXMB to search for Blac inhibitors from herbal medicines. Tannic acid was identified as a potential Blac inhibitor and showed enhanced inhibitory effects when combined with β-lactam antibiotics against M. tuberculosis H37Ra. This research provides valuable insights into the mechanism of drug resistance and contributes to the development of new TB treatments.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Biochemistry & Molecular Biology
Senhao Xiao, Siqi Guo, Jie Han, Yanli Sun, Mingchen Wang, Yantao Chen, Xueyu Fang, Feng Yang, Yajuan Mu, Liang Zhang, Yiluan Ding, Naixia Zhang, Hualiang Jiang, Kaixian Chen, Kehao Zhao, Cheng Luo, Shijie Chen
Summary: This study developed a fluorescence polarization-based assay for high-throughput screening and evaluation of enzymatic activity of DNA/RNA methyltransferases and demethylases. The assay is simple, sensitive, and quick.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Physical
Surender Mohan, Dhananjay Jade, Sonal Gupta, Selvaraj Ayyamperumal, M. J. N. Chandrasekar, M. J. Nanjan
Summary: This study developed potential inhibitors for Mycobacterium tuberculosis (Mtb) by targeting the alpha-subunit of tryptophan synthase (TRPS). After screening and calculations, five compounds with potential were selected for further preclinical testing.
MOLECULAR SIMULATION
(2022)
Article
Chemistry, Medicinal
Sandra Johannsen, Robin M. Gierse, Aleksandra Olshanova, Ellie Smerznak, Christian Laggner, Lea Eschweiler, Zahra Adeli, Rawia Hamid, Alaa Alhayek, Norbert Reiling, Joerg Haupenthal, Anna K. H. Hirsch
Summary: This work emphasizes the importance of investigating both on-target activity and antibiotic activity against critical pathogens. The authors focused on the 1-deoxy-d-xylulose 5-phosphate synthase (DXPS) as a potential new target and conducted virtual screening and activity studies. While no improvement in activity was observed in the synthesized derivatives, they found that the compounds showed good inhibition against Escherichia coli in their tests against various pathogens.
Article
Chemistry, Multidisciplinary
Di Zhu, Sandra Johannsen, Tiziana Masini, Celine Simonin, Jorg Haupenthal, Boris Illarionov, Anastasia Andreas, Mahendra Awale, Robin M. Gierse, Tridia van der Laan, Ramon van der Vlag, Rita Nasti, Mael Poizat, Eric Buhler, Norbert Reiling, Rolf Mueller, Markus Fischer, Jean-Louis Reymond, Anna K. H. Hirsch
Summary: In this manuscript, the authors successfully used ligand-based virtual screening (LBVS) to identify two small-molecule drug-like hit classes with excellent ADMET profiles against the challenging microbial enzyme DXPS. They introduced the concept of pseudo-inhibitors to overcome the limitations of standard computer-aided drug design tools for targets with large, hydrophilic binding sites. The hits displayed promising in vitro and whole-cell activity against M. tuberculosis DXPS, and possess unique mechanisms of inhibition, making them potential starting points for the development of antibiotics with a novel mode of action.
Review
Biochemistry & Molecular Biology
Eva Pauwels, Ralf Schuelein, Kurt Vermeire
Summary: The process of protein translocation across the ER is mediated by the Sec61 translocon complex, which is challenging to purify and reconstitute, making it difficult to screen for small molecule inhibitors. However, these inhibitors have potential as valuable tools in cell biology and as novel anticancer drugs. Recent screening strategies may also help in identifying new antibiotic drugs targeting the bacterial Sec61 complex counterpart, SecYEG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Sadaf Kalsum, Blanka Andersson, Jyotirmoy Das, Thomas Schon, Maria Lerm
Summary: The study demonstrates the effectiveness of using automated live-cell imaging to monitor different growth phenotypes of Mycobacterium tuberculosis and evaluate their susceptibility to anti-TB drugs. Results show that the cording phenotype is more susceptible to drugs like rifampicin, indicating the potential advantage of this method in screening and evaluating anti-tuberculosis drugs.
Article
Biochemistry & Molecular Biology
Jordan T. Koehn, Cheryle N. Beuning, Benjamin J. Peters, Sara K. Dellinger, Cameron Van Cleave, Dean C. Crick, Debbie C. Crans
Article
Multidisciplinary Sciences
Un Yung Choi, Jae Jin Lee, Angela Park, Wei Zhu, Hye-Ra Lee, Youn Jung Choi, Ji-Seung Yoo, Claire Yu, Pinghui Feng, Shou-Jiang Gao, Shaochen Chen, Hyungjin Eoh, Jae U. Jung
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Microbiology
B. Luna, V Trebosc, B. Lee, M. Bakowski, A. Ulhaq, J. Yan, P. Lu, J. Cheng, T. Nielsen, J. Lim, W. Ketphan, H. Eoh, C. McNamara, N. Skandalis, R. She, C. Kemmer, S. Lociuro, G. E. Dale, B. Spellberg
NATURE MICROBIOLOGY
(2020)
Article
Chemistry, Medicinal
Santosh Kumar, Jordan T. Koehn, Mercedes Gonzalez-Juarrero, Debbie C. Crans, Dean C. Crick
ACS INFECTIOUS DISEASES
(2020)
Article
Chemistry, Medicinal
Fabio L. Fontes, Benjamin J. Peters, Debbie C. Crans, Dean C. Crick
ACS INFECTIOUS DISEASES
(2020)
Article
Multidisciplinary Sciences
Juhyeon Lim, Jae Jin Lee, Sun-Kyung Lee, Seoyong Kim, Seok-Yong Eum, Hyungjin Eoh
Summary: The nonreplicating state of Mycobacterium tuberculosis undergoes metabolic remodeling, with the depletion of phosphoenolpyruvate (PEP) leading to drug resistance, while supplementation with PEP restores drug sensitivity, preventing the emergence of drug-resistant strains.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Hojae Lee, Jae Jin Lee, Na Young Park, Sandeep Kumar Dubey, Taeyong Kim, Kai Ruan, Su Bin Lim, Seong-Hyun Park, Shinwon Ha, Irina Kovlyagina, Kyung-tai Kim, Seongjun Kim, Yohan Oh, Hyesoo Kim, Sung-Ung Kang, Mi-Ryoung Song, Thomas E. Lloyd, Nicholas J. Maragakis, Young Bin Hong, Hyungjin Eoh, Gabsang Lee
Summary: By comparing human induced pluripotent stem cell-derived spinal and ocular motor neurons, researchers identified low levels of a natural 5-lipoxygenase inhibitor in ALS spinal motor neurons and found that analogs of 5-lipoxygenase inhibitors can improve ALS phenotypes. Multi-omics analysis revealed shared metabolic perturbations in ALS spinal motor neurons, specifically dysregulation in lipid metabolism, which was confirmed through targeted metabolomics. These findings highlight a potential therapeutic target in lipid metabolism for ALS.
NATURE NEUROSCIENCE
(2021)
Article
Microbiology
Camila G. Quinonez, Jae Jin Lee, Juhyeon Lim, Mark Odell, Christopher P. Lawson, Amararachukwu Anyogu, Saki Raheem, Hyungjin Eoh
Summary: The fatty acid-induced dormancy-like state remodels the central carbon metabolism of Mycobacterium tuberculosis, enhancing its drug tolerance. This finding is important for understanding the adaptive strategies of M. tuberculosis and for the development of new drugs.
Article
Gastroenterology & Hepatology
Young Jae Kim, June-Young Lee, Jae Jin Lee, Sang Min Jeon, Prashanta Silwal, In Soo Kim, Hyeon Ji Kim, Cho Rong Park, Chaeuk Chung, Jeong Eun Han, Jee-Won Choi, Euon Jung Tak, Ji-Ho Yoo, Su-Won Jeong, Do-Yeon Kim, Warisa Ketphan, Su-Young Kim, Byung Woo Jhun, Jake Whang, Jin-Man Kim, Hyungjin Eoh, Jin-Woo Bae, Eun-Kyeong Jo
Summary: The study demonstrates that l-arginine enhances pulmonary immune defense against nontuberculous mycobacterial pulmonary diseases (NTM-PD) by influencing the gut-lung axis, increasing the number of IFN-gamma-producing effector T cells and M1 macrophages in the lungs, and enhancing antimicrobial activity.
Article
Cell Biology
Camila G. Quinonez, Jae Jin Lee, Juhyeon Lim, Mark Odell, Christopher P. Lawson, Amarachukwu Anyogu, Saki Raheem, Hyungjin Eoh
Summary: Unlike other bacteria, Mycobacterium tuberculosis has the ability to utilize host fatty acids as a carbon source, which contributes to its pathogenicity and drug tolerance. Identifying key enzymes involved in fatty acid metabolism is important for new drug development. Recent research has shown a link between fatty acid-induced dormancy-like state and drug tolerance via dysregulated MCC activity.
Article
Cell Biology
Un Yung Choi, Jae Jin Lee, Angela Park, Kyle L. Jung, Shin-Ae Lee, Youn Jung Choi, Hye-Ra Lee, Chih-Jen Lai, Hyungjin Eoh, Jae U. Jung
Summary: KSHV hijacks spermidine synthesis and eIF5A hypusination pathways to enhance LANA expression for viral episomal maintenance, suggesting polyamine metabolism and eIF5A hypusination as therapeutic targets for KSHV-induced tumorigenesis.
Review
Immunology
Hyungjin Eoh, Rachel Liu, Juhyeon Lim, Jae Jin Lee, Philip Sell
Summary: The suboptimal efficacy of current antibiotic regimens and frequent emergence of antibiotic-resistant Mycobacterium tuberculosis (Mtb) require the identification of new antibiotic targets. Metabolomics provides valuable insights into the mechanisms of drug tolerance and resistance, and offers unique advantages over other techniques.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Go Sugahara, Yuji Ishida, Jae Jin Lee, Meng Li, Yasuhito Tanaka, Hyungjin Eoh, Yusuke Higuchi, Takeshi Saito
Summary: This study aimed to define the environmental requirements necessary for maintaining the homeostasis of terminally differentiated hepatocytes. The supplementation of dimethyl sulfoxide (DMSO) was found to be indispensable for mitigating fate deterioration and promoting adaptation to the in vitro environment. Dimethyl sulfone (DMSO2) was identified as a substitute for DMSO, supporting the long-term maintenance of hepatocyte morphology, marker gene expression, and functionality.
Article
Microbiology
Ritu Sharma, Travis E. Hartman, Tiago Beites, Jee-Hyun Kim, Hyungjin Eoh, Curtis A. Engelhart, Linnan Zhu, Daniel J. Wilson, Courtney C. Aldrich, Sabine Ehrt, Kyu Young Rhee, Dirk Schnappinger
Summary: The current treatment for tuberculosis (TB) infections is lengthy and requires multiple antibiotics. The development of shorter, simpler treatment regimens is critical to eradicating TB. NadE, an enzyme essential for the synthesis of the cofactor NAD, is considered a promising drug target. Through gene silencing and metabolomics, it has been shown that NADP deficiency is bacteriostatic, while NAD deficiency is bactericidal due to its role in Mtb's respiratory capacity. These findings suggest prioritizing NAD biosynthesis inhibitors in anti-TB drug development.
Article
Microbiology
Camila G. Quinonez, Jae Jin Lee, Juhyeon Lim, Mark Odell, Christopher P. Lawson, Amararachukwu Anyogu, Saki Raheem, Hyungjin Eoh
Summary: This study reveals the metabolic changes of fatty acid-induced dormancy-like state of Mycobacterium tuberculosis and its involvement in the acquisition of drug tolerance. Mutant strains lacking MCC enzymes show different levels of drug tolerance, indicating the importance of MCC intermediates in drug tolerance mechanisms.
