Article
Multidisciplinary Sciences
Tahmina Hossain, Heather S. Deter, Eliza J. Peters, Nicholas C. Butzin
Summary: Antibiotic persistence plays a significant role in the evolution of antibiotic resistance and relapsing infections. The minimal cell Mycoplasma mycoides JCVI-Syn3B evolves antibiotic resistance quickly to different types of antibiotics and exhibits tolerance and persistence against multiple antibiotics.
Article
Immunology
Yingjie Song, Hong Tang, Rui Bao
Summary: This study investigated the diversity and function of five genomic type II TA systems in Pseudomonas aeruginosa clinical isolates and their impact on the persistence and invasion ability of the bacteria. The PA1030/PA1029 and HigBA TA systems were found to be critical for intracellular survival and could be potential targets for novel antibiotic treatments.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Microbiology
Chun-Yi Lin, Sanya Hamini, Peter Robert Tupa, Hisako Masuda
Summary: The length of growth arrest induced by HipA depends on environmental factors, especially the past growth environment of cells, and decreases with multiple cycles of induction.
Article
Biochemistry & Molecular Biology
Shobhi Chaudhary, Mohit Yadav, Shalini Mathpal, Subhash Chandra, Jitendra Singh Rathore
Summary: This study explores the genomic assortment, structural and functional association of chromosomally encoded ccdAB TA homolog (ccdAB(Xn)(1)) in Xenorhabdus nematophila. The results suggest that there is no closer relationship between the antitoxin and toxin parts, and they may affect cellular metabolism.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Microbiology
Laura Fernandez-Garcia, Sooyeon Song, Joy Kirigo, Michael E. Battisti, Maiken E. Petersen, Maria Tomas, Thomas K. Wood
Summary: This study reveals that bacteria can defend against phage infection by forming persister cells instead of inducing cell suicide. Furthermore, the restriction/modification systems work together with the toxin/antitoxin system to clear phage DNA. These findings are crucial for the success of phage therapy.
MICROBIOLOGY SPECTRUM
(2023)
Article
Multidisciplinary Sciences
Fatema Calcuttawala, Rahul Shaw, Arpita Sarbajna, Moumita Dutta, Saptarshi Sinha, Sujoy K. Das Gupta
Summary: This study investigated the mechanism of mycobacteriophage infection in Mycobacterium smegmatis cells, revealing that high VapC may play a role in inducing apoptotic cell death in mycobacteria. The research demonstrated morphological and molecular changes indicative of apoptotic cell death caused by D29 infection.
Article
Multidisciplinary Sciences
Fatema Calcuttawala, Rahul Shaw, Arpita Sarbajna, Moumita Dutta, Saptarshi Sinha, Sujoy K. Das Gupta
Summary: The study found that infection by mycobacteriophages causes mycobacteria to undergo apoptotic cell death. Researchers observed the details of the infection process and the morphological and molecular changes associated with cell death using immunofluorescence and electron microscopy techniques.
Article
Microbiology
Qibing Gu, Peijuan He, Dan Wang, Jiale Ma, Xiaojun Zhong, Yinchu Zhu, Yue Zhang, Qiankun Bai, Zihao Pan, Huochun Yao
Summary: The Xress-MNTss TA system was discovered in Streptococcus suis, playing a crucial role in antibiotic resistance and pathogenicity. The Xress deletion mutant showed lower pathogenicity in mice but had a stronger capacity for biofilm formation compared to the wild-type strain. These findings suggest that the Xress-MNTss TA system is important in S. suis.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Tatsuaki Kurata, Chayan Kumar Saha, Jessica A. Buttress, Toomas Mets, Tetiana Brodiazhenko, Kathryn J. Turnbull, Ololade F. Awoyomi, Sofia Raquel Alves Oliveira, Steffi Jimmy, Karin Ernits, Maxence Delannoy, Karina Persson, Tanel Tenson, Henrik Strahl, Vasili Hauryliuk, Gemma C. Atkinson
Summary: Toxin-antitoxin gene pairs are widespread in microorganisms and bacteriophages, acting as regulatory switches. A computational tool called FlaGs was used to analyze the conservation of genomic neighborhoods and uncover previously unknown diversity in TA operons. The poorly characterized antitoxin domain DUF4065 was found to be widely distributed and capable of neutralizing toxins with multiple different folds. Experimental validation confirmed the neutralizing activity of nine PanA-neutralized TA pairs, including a novel nucleotide cyclase toxin. Panacea-containing antitoxins were found to form complexes with their cognate toxins, indicating a direct neutralization mechanism. Directed evolution also demonstrated the evolutionary plasticity of the PanA antitoxin domain.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Clinton C. Dawson, Jason E. Cummings, Julie M. Starkey, Richard A. Slayden
Summary: This study reports the discovery of a novel antisense RNA, called asRelE2, which co-regulates the production of RelE2. It also found that the essential cAMP receptor protein transcription factor, Crp, controls the convergent expression of the coding-antisense hybrid TA locus under host-associated stress conditions.
MOLECULAR MICROBIOLOGY
(2022)
Article
Immunology
Mohit Yadav, Jitendra Singh Rathore
Summary: This study investigates the functionality and transcriptional regulation of the type II hipBA(Xn2) TA system in X. nematophila. The results provide evidence for the presence of a well-regulated TA system that is involved in maintaining genomic stability and survival under stress conditions.
MICROBIAL PATHOGENESIS
(2022)
Article
Microbiology
Wonho Choi, Anoth Maharjan, Hae Gang Im, Ji-Young Park, Jong-Tae Park, Jung-Ho Park
Summary: Toxin-antitoxin (TA) systems, which regulate various cellular processes, are prevalent in bacteria and archaea. In this study, the MTH463/MTH464 TA system from Methanothermobacter thermautotropicus ?H was characterized. MTH463 was shown to inhibit the growth of Escherichia coli, while MTH464 blocked the activity of MTH463. Mutagenesis experiments revealed specific amino acids involved in the toxicity of MTH463. Furthermore, purified MTH463 was able to degrade phage RNA, while purified MTH464 neutralized the activity of MTH463 in vitro. These findings suggest that MTH463 and MTH464 function as a type II TA system in M. thermautotropicus ?H.
JOURNAL OF MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shaun Wachter, Diane C. C. Cockrell, Heather E. E. Miller, Kimmo Virtaneva, Kishore Kanakabandi, Benjamin Darwitz, Robert A. A. Heinzen, Paul A. A. Beare
Summary: This study investigates the role of plasmid-encoded ORFs in Coxiella burnetii, particularly the importance of the QpH1 plasmid for its virulence. The findings suggest that C. burnetii maintains autonomously replicating plasmids due to the presence of a plasmid-based toxin-antitoxin system.
MOLECULAR MICROBIOLOGY
(2022)
Article
Immunology
Itziar Chapartegui-Gonzalez, Nittaya Khakhum, Jacob L. Stockton, Alfredo G. Torres
Summary: Melioidosis, caused by Burkholderia pseudomallei, is an underreported human disease with challenging treatment and clearance. This study reveals the association between bacterial persistence and toxin-antitoxin systems, specifically the HigB toxin and its HigA antitoxin, in the context of levofloxacin-induced persister conditions.
INFECTION AND IMMUNITY
(2022)
Article
Chemistry, Medicinal
Hongmao Sun, Nathan P. Coussens, Carina Danchik, Leah M. Wachsmuth, Mark J. Henderson, Samarjit Patnaik, Matthew D. Hall, Ashley L. Molinaro, Dayle A. Daines, Min Shen
Summary: This study identified potential inhibitors of NTHi VapC1 ribonuclease through virtual screening and scaffold hopping. These inhibitors could serve as starting points for preclinical development.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Juan Xie, Shiwei Wang, Youjun Xu, Minghua Deng, Luhua Lai
Summary: This study analyzed dominant motion modes to determine motion correlations between allosteric and orthosteric sites, finding that such correlations are dominated by either fast or slow vibrational modes. The developed prediction tool CorrSite2.0 outperformed other methods in predicting allosteric sites, providing a powerful tool for allosteric drug and protein design.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Xiaodong Dou, Qi Sun, Guofeng Xu, Yameng Liu, Caifang Zhang, Bingding Wang, Yangbin Lu, Zheng Guo, Lingyu Su, Tongyu Huo, Xinyi Zhao, Chen Wang, Zhongtian Yu, Song Song, Liangren Zhang, Zhenming Liu, Luhua Lai, Ning Jiao
Summary: This study reported novel non-peptidomimetic inhibitors of SARS-CoV-2 Mpro developed through in-house library screening and biological evaluation. The compounds showed high inhibitory activity and low cytotoxicity, providing a promising starting point for further drug development and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Weixin Xie, Fanhao Wang, Yibo Li, Luhua Lai, Jianfeng Pei
Summary: This article highlights the latest developments in using deep learning techniques combined with 3D molecular generative models for de novo drug design, and discusses future research directions.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Cell Biology
Rong Hu, Umar Farook Shahul Hameed, Xiang Sun, Balakrishnan Shenbaga Moorthy, Wen Zhang, Philip D. Jeffrey, Li Zhou, Xin Ma, Fangjin Chen, Jianfeng Pei, Pankaj K. Giri, Yonggao Mou, Kunchithapadam Swaminathan, Ping Yuan
Summary: Peptide LSD1-197-211 can repress BTICs by interfering the synergistic function of NR2E1 and LSD1 and may be a promising lead peptide for brain tumour therapy in future.
CELL PROLIFERATION
(2023)
Article
Biochemistry & Molecular Biology
Chenjing Cai, Haoyu Lin, Hongyi Wang, Youjun Xu, Qi Ouyang, Luhua Lai, Jianfeng Pei
Summary: The drug development pipeline consists of in vitro assays, in vivo assays, and clinical trials. We developed three subdivisional models using graph neural networks to predict the compound's capacity to pass through the in vivo testing, clinical trials, and market approval stages. By combining active learning and ensemble learning, we improved the quality of the models and achieved satisfactory performance in internal and external test datasets. Our model system, miDruglikeness, also showed a powerful ability in virtual screening tasks, providing a comprehensive drug-likeness prediction tool for drug discovery and development.
Article
Chemistry, Physical
Juan Xie, Gaoxiang Pan, Yibo Li, Luhua Lai
Summary: This study demonstrates the importance of protein topology in allosteric regulation, showing that allosteric proteins mainly have multiple domains or subunits, and allosteric sites are often located between domains of the same fold type. A novel method, called TopoAlloSite, was developed to predict the location of allosteric sites on protein topology, successfully identifying cryptic allosteric sites in several proteins. This research provides insights for finding new druggable targets and designing allosteric drugs.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Virology
Zhao-Xi Wang, Bing Liu, Tian Yang, Daqi Yu, Chu Zhang, Liming Zheng, Jin Xie, Bin Liu, Mengxi Liu, Hailin Peng, Luhua Lai, Qi Ouyang, Songying Ouyang, Yong-An Zhang
Summary: Aquaculture accounts for 70% of global aquatic products, but viral diseases are a major problem. SVCV causes a highly contagious disease in common carp, but there are no vaccines or effective treatments. This study resolved the structure of SVCV ribonucleoprotein complex (RNP) and screened antiviral drugs based on this structure, finding that suramin has good antiviral effects.
JOURNAL OF VIROLOGY
(2023)
Article
Chemistry, Multidisciplinary
Shuai Liu, Xiangyu Sun, Huan Lu, Daiqin Chen, Xue Li, Lei Li, Shenge Su, Zhongpu Zhao, Xinran Cao, Libing Liu, Luhua Lai, Xueguang Lu, Chunying Shu, Chunru Wang, Chunli Bai
Summary: A fullerene-based nanocomplex was designed for the inhalation delivery of siRNA, which protects siRNA against degradation, improves cellular uptake and gene knockdown efficiency, and prolongs pulmonary retention. By packaging PD-L1 siRNA, this nanocomplex significantly inhibits the progression of metastatic lung cancer in a mouse model without obvious adverse events and toxicity. This fullerene-based nanocomplex opens up the possibility of siRNA for treating a diverse range of pulmonary diseases.
Article
Biology
He-Wei Jiang, Hong Chen, Yun-Xiao Zheng, Xue-Ning Wang, Qingfeng Meng, Jin Xie, Jiong Zhang, ChangSheng Zhang, Zhao-Wei Xu, Zi-Qing Chen, Lei Wang, Wei-Sha Kong, Kuan Zhou, Ming-Liang Ma, Hai-Nan Zhang, Shu-Juan Guo, Jun-Biao Xue, Jing-Li Hou, Zhe-Yi Liu, Wen-Xue Niu, Fang-Jun Wang, Tao Wang, Wei Li, Rui-Na Wang, Yong-Jun Dang, Daniel M. Czajkowsky, JianFeng Pei, Jia-Jia Dong, Sheng-Ce Tao
Summary: Protein-biomolecule interactions are important in biological processes, and the identification of interacting proteins is crucial. The SPIDER method, combining proximity labeling activity and streptavidin-biotin system, successfully validated known protein-DNA, protein-RNA, and protein-small molecule interactions. It was also used to construct global protein interactomes for m(6)A and mRNA, identify unknown m(6)A binding proteins, and validate SRSF7 as a potential m(6)A reader. Furthermore, SPIDER identified binding proteins for lenalidomide and CobB, as well as SARS-CoV-2-specific receptors on cell membranes.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Article
Endocrinology & Metabolism
Jianfeng Pei, Yanyun Li, Yihui Yang, Minna Cheng, Yan Shi, Wang Hong Xu
Summary: The prevalence of diabetes and prediabetes among Chinese adults in Shanghai has been increasing over the years, leading to a heavier disease burden. The study emphasizes the urgent need to strengthen the community healthcare system in China to ensure comprehensive management of diabetes and prediabetes.
JOURNAL OF DIABETES
(2023)
Article
Biology
Juan Xie, Weilin Zhang, Xiaolei Zhu, Minghua Deng, Luhua Lai, Shozeb Haider
Summary: Allostery plays a fundamental role in biological processes, but predicting the impact of allosteric mutations, modifications, and effector binding on protein function is challenging. We developed a novel computational method, KeyAlloSite, to predict allosteric sites and identify key allosteric residues based on the evolutionary coupling model. Our predictions are consistent with previous experimental studies and key cancer mutations. KeyAlloSite can be applied in studying the evolution of protein allosteric regulation, designing and optimizing allosteric drugs, and performing functional protein design and enzyme engineering.
Editorial Material
Chemistry, Multidisciplinary
Jintao Zhu, Luhua Lai, Jianfeng Pei
ACS CENTRAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Xiaoyu Qing, Qian Wang, Hanyu Xu, Pei Liu, Luhua Lai
Summary: Loop epitopes at protein-protein binding interfaces are underexplored as drug targets due to their high flexibility, relatively few hot spots, and solvent accessibility. However, this study demonstrates that cyclic peptides derived from loop epitopes can inhibit protein activity by directly binding to the dimer interface and disrupting the oligomer formation. These findings suggest that rationally designed cyclic peptides can modulate protein oligomers and be used to design inhibitors for other seemingly intractable oligomeric proteins.