Article
Microbiology
Suresh Kumar, Mehak Zahoor Khan, Neha Khandelwal, Chen Chongtham, Biplab Singha, Ankita Dabla, Debashree Behera, Archana Singh, Balasubramanian Gopal, G. Aneeshkumar Arimbasseri, Siddhesh S. Kamat, Vinay Kumar Nandicoori
Summary: EmbR, a transcription factor, plays crucial roles in modulating cellular morphology, antibiotic resistance, and survival in the host. The study highlights EmbR as a key regulator of the hypoxic response in mycobacterial survival.
Article
Critical Care Medicine
Allison N. Bucsan, Ashley Veatch, Dhiraj K. Singh, Sadia Akter, Nadia A. Golden, Melanie Kirkpatrick, Breanna Threeton, Chivonne Moodley, Mushtaq Ahmed, Lara A. Doyle, Kasi Russell-Lodrigue, Elizabeth B. Norton, Peter J. Didier, Chad J. Roy, Robert B. Abramovitch, Smriti Mehra, Shabaana A. Khader, Deepak Kaushal
Summary: The response to hypoxia is a critical factor in determining the virulence of Mycobacterium tuberculosis (Mtb). The Erdman strain of Mtb showed higher hypoxia induction, leading to faster replication, more severe pathology, and larger necrotic regions compared to the CDC1551 strain.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Akhil Raj Pushparajan, Lekshmi K. Edison, Ramakrishnan Ajay Kumar
Summary: The main obstacle in eradicating tuberculosis is the ability of Mycobacterium tuberculosis to remain dormant in the host and reactivate later under immunocompromised conditions. This study shows that the transcriptional regulator Rv1019 plays a role in regulating the expression of several genes, including those involved in the biosynthesis of oleic acid.
Review
Immunology
Paolo Miotto, Rita Sorrentino, Stefano De Giorgi, Roberta Provvedi, Daniela Maria Cirillo, Riccardo Manganelli
Summary: Bacterial drug resistance poses a serious threat to human health, with tuberculosis being a high-risk infection due to limited drugs available against Mycobacterium tuberculosis. Drug resistance in bacteria is often caused by point mutations in drug targets, but changes in transcriptional regulation post-drug exposure also play a significant role and should be further explored for potential new drug targets and intervention strategies.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Danicke Willemse, Chivonne Moodley, Smriti Mehra, Deepak Kaushal
Summary: Smoking is a known added risk factor for tuberculosis, increasing the risk of active TB and reducing cure and treatment completion rates. Cigarette smoke contains harmful compounds that may potentially enhance the virulence of the tubercle bacilli. Further research is needed to explore the impact of cigarette smoke on Mycobacterium tuberculosis and its potential implications for TB treatment efficacy.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Sebastian F. Zenk, Sebastian Hauck, Daniel Mayer, Mark Grieshober, Steffen Stenger
Summary: Hypoxia-inducible factor (HIF) plays a crucial role in regulating cellular metabolism in response to a low oxygen environment, and stabilizing HIF can enhance host antimicrobial activity against tuberculosis. Inhibition of prolyl-hydroxylases by Molidustat further induces specific immune effectors, reducing the proliferation of intracellular mycobacteria in human macrophages. These findings suggest that HIFs may be promising targets for host-directed therapy against infectious diseases like tuberculosis caused by intracellular bacteria.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Catherine Vilcheze, Bo Yan, Rosalyn Casey, Suzie Hingley-Wilson, Laurence Ettwiller, William R. Jacobs
Summary: This study provides detailed insights into the transcriptome changes of Mycobacterium tuberculosis under persisting stresses, highlighting genes and gene cohorts involved in stress response. These findings are valuable for the design of novel drug targets and vaccine development.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Amelia E. Hinman, Charul Jani, Stephanie C. Pringle, Wei R. Zhang, Neharika Jain, Amanda J. Martinot, Amy K. Barczak
Summary: The study identified that phagosomal membrane damage caused by Mtb benefits invading pathogens by enhancing a late TLR2-dependent transcriptional response, which interferes with effective inflammation generation and promotes tuberculosis pathogenesis in both macrophage and murine infection models.
Review
Immunology
Amanda N. N. Samuels, Erin R. R. Wang, Gregory A. A. Harrison, Joy C. C. Valenta, Christina L. L. Stallings
Summary: This article discusses the impact of bacterial central carbon metabolism on Mtb drug tolerance and proposes that these metabolic pathways could be potential drug targets. By better understanding the physiological state of Mtb in the host, we can hope to treat tuberculosis more effectively.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Elizabeth A. Wynn, Christian Dide-Agossou, Matthew Reichlen, Karen Rossmassler, Reem Al Mubarak, Justin J. Reid, Samuel T. Tabor, Sarah E. M. Born, Monica R. Ransom, Rebecca M. Davidson, Kendra N. Walton, Jeanne B. Benoit, Amanda Hoppers, Dorothy E. Loy, Allison A. Bauman, Lisa M. Massoudi, Gregory Dolganov, Michael Strong, Payam Nahid, Martin I. Voskuil, Gregory T. Robertson, Camille M. Moore, Nicholas D. Walter
Summary: To address the global tuberculosis crisis, this study aimed to develop shorter and more effective treatments. A novel RNA-seq method called SEARCH-TB was used to investigate the transcriptome of Mycobacterium tuberculosis in mice treated with standard drugs for up to 28 days. The results showed that treatment suppressed genes related to growth, transcription, translation, protein synthesis, and immunogenicity, while bacteria that survived prolonged treatment exhibited cellular adaptations including changes in respiration, modification and recycling of cell wall components, and large-scale regulatory reprogramming.
Article
Immunology
Jing Wei, Fangzheng Guo, Yamin Song, Kun Xu, Feiyang Lin, Kangsheng Li, Baiqing Li, Zhongqing Qian, Xiaojing Wang, Hongtao Wang, Tao Xu
Summary: In this study, RNA sequencing of Mtb-Ag-stimulated and control samples identified differentially expressed genes related to immune function. These genes are primarily involved in cellular pathways associated with immune function, revealing the immune response mechanism triggered by Mtb-Ag stimulation.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Ying Zhou, Tianying Zhong, Wenjing Wei, Zhuhua Wu, Anping Yang, Ning Liu, Ming Wang, Xiaoli Zhang
Summary: The study characterized the impact of downregulating Mtsp17 on gene expression in Myobacterium smegmatis, revealing that Mtsp17 may act as an activator of desA1 and regulate the SigF regulon through the SigF regulatory pathway. This sheds light on the transcriptional regulation role of Mtsp17 and provides new insights into the molecular mechanisms of START family proteins.
Article
Microbiology
Kayvan Zainabadi, Kohta Saito, Saurabh Mishra, Kathleen Frances Walsh, Laurent Daniel Mathurin, Stalz Charles Vilbrun, Oksana Ocheretina, Jean William Pape, Daniel W. Fitzgerald, Carl F. Nathan, Myung Hee Lee
Summary: Certain populations of Mycobacterium tuberculosis that cannot be detected by standard diagnostics have been studied using limiting dilution assays. This study aimed to understand the similarity between in vitro models and patient sputum in terms of differential detection of Mycobacterium tuberculosis populations. Gene expression analysis revealed that the expression of certain genes correlated with the abundance of differential detectable Mycobacterium tuberculosis. The use of these gene profiles may facilitate the monitoring of Mycobacterium tuberculosis populations in patient sputum.
Article
Microbiology
Kayvan Zainabadi, Kohta Saito, Saurabh Mishra, Kathleen Frances Walsh, Laurent Daniel Mathurin, Stalz Charles Vilbrun, Oksana Ocheretina, Jean William Pape, Daniel W. Fitzgerald, Carl F. Nathan, Myung Hee Lee
Summary: This study evaluated the correlation between a new in vitro model of Mycobacterium tuberculosis and the presence of differentially detectable (DD) M. tuberculosis in patient sputum. The study found that the model resembled DD M. tuberculosis found in patients and that the expression of certain genes correlated with the presence and abundance of DD M. tuberculosis. These findings suggest that transcriptional profiles of DD M. tuberculosis may be useful for monitoring the population in patient sputum.
Article
Biochemistry & Molecular Biology
Shuangquan Yan, Junfeng Zhen, Yuzhu Li, Yu Huang, Xuefeng Ai, Yue Li, Andrea Stojkoska, Xue Huang, Cao Ruan, Jiang Li, Lin Fan, Jianping Xie
Summary: This study identified M. smegmatis MSMEG_1415 as an arginine-responsive transcription factor regulating the arginase pathway, which is activated in the presence of L-arginine. The research revealed a unique regulatory mechanism of arginine metabolism in mycobacteria and suggested M. tb Rv2324 as a potential target for drug design against tuberculosis.
JOURNAL OF GENETICS AND GENOMICS
(2021)
Article
Microbiology
Ding-qian Liu, Jun-li Zhang, Zhi-fen Pan, Jun-tao Mai, Heng-jun Mei, Yue Dai, Lu Zhang, Qing-zhong Wang
INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY
(2020)
Article
Genetics & Heredity
Jun Jiang, Chen Lin, Junli Zhang, Yuchen Wang, Lifang Shen, Kunpeng Yang, Wenxuan Xiao, Yao Li, Lu Zhang, Jun Liu
FRONTIERS IN GENETICS
(2020)
Review
Biochemistry & Molecular Biology
Shuqin Xu, Kunpeng Yang, Rose Li, Lu Zhang
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Pharmacology & Pharmacy
Jacqueline Watt, Jun Liu
Article
Biophysics
Qiran Zhai, Chen Lin, Bo Duan, Jun Liu, Lu Zhang, Bin Xia
Summary: WhiB4 protein, a member of the WhiB-like protein family, plays a crucial role in the survival and pathology of Mycobacterium tuberculosis. Acting as a transcription factor, WhiB4 regulates genes involved in redox balance, central metabolism, and respiration. It exists in different forms under different redox environments, including a dimeric holo form with iron-sulfur cluster, multimeric disulfide-linked oxidized apo forms, and a monomeric reduced apo form.
BIOMOLECULAR NMR ASSIGNMENTS
(2021)
Article
Multidisciplinary Sciences
Hui Guo, Gautier M. Courbon, Stephanie A. Bueler, Juntao Mai, Jun Liu, John L. Rubinstein
Summary: The study of the ATP synthase structures in Mycobacterium smegmatis has provided insights into how the enzyme conserves energy through autoinhibition of ATP hydrolysis and the mechanism of action of the drug bedaquiline used in treating multidrug-resistant tuberculosis. Tuberculosis, caused by Mycobacterium tuberculosis, is increasingly resistant to first-line antibiotics, allowing infections to remain dormant and decreasing susceptibility to many antibiotics. Bedaquiline, developed from a lead compound identified in a screen against Mycobacterium smegmatis, targets the mycobacterial ATP synthase and is a cornerstone in the treatment of multidrug-resistant and extensively drug-resistant tuberculosis.
Review
Biochemistry & Molecular Biology
Bo Duan, Pengfei Ding, William Wiley Navarre, Jun Liu, Bin Xia
Summary: Horizontal gene transfer (HGT) is a major driving force for bacterial evolution, with xenogeneic silencers playing a crucial role in recognizing and suppressing foreign genes to maintain genomic stability. The diversity in DNA recognition mechanisms of xenogeneic silencers leads to clear characteristics in DNA sequence preferences, correlated with different host genomic features. Xenogeneic silencers also act as a selective force against GC to AT mutational bias in bacterial genomes and help maintain host genomic AT contents at relatively low levels.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Biochemistry & Molecular Biology
Huibi Cao, Juntao Mai, Zhichang Zhou, Zhijie Li, Rongqi Duan, Jacqueline Watt, Ziyan Chen, Ranmal Avinash Bandara, Ming Li, Sang Kyun Ahn, Betty Poon, Natasha Christie-Holmes, Scott D. Gray-Owen, Arinjay Banerjee, Karen Mossman, Rob Kozak, Samira Mubareka, James M. Rini, Jim Hu, Jun Liu
Summary: In this study, a novel intranasal COVID-19 vaccine based on a helper-dependent adenoviral vector has been described. The vaccine induces robust mucosal and systemic immunity and provides complete protection of the upper respiratory tract against SARS-CoV-2 infection in mice. This approach shows promise in developing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.
CELL AND BIOSCIENCE
(2021)
Article
Multidisciplinary Sciences
Yuchen Wang, Yuting Tang, Chen Lin, Junli Zhang, Juntao Mai, Jun Jiang, Xiaoxiao Gao, Yao Li, Guoping Zhao, Lu Zhang, Jun Liu
Summary: The ESX-4 system in Mycobacterium marinum does not secrete its cognate substrates, but the deletion of eccC4, an essential component of ESX-4, resulted in elevated secretion of protein substrates of ESX-1 and ESX-5, leading to enhanced phagocytosis by macrophages.
Article
Immunology
Jingrui Song, Jin Chao, Xiaohong Hu, Xin Wen, Cairong Ding, Dan Li, Ding Zhang, Shanshan Han, Xiang Yu, Bo Yan, Zhu Jin, Yinhong Song, Jacqueline Gonzales, Laura E. Via, Lu Zhang, Decheng Wang
Summary: This study reveals a previously unknown role of FBXW7 in regulating TNF-alpha dynamics during mycobacterial infection. Upregulation of FBXW7 in macrophages infected with Mm inhibits TNF-alpha production, contributing to bacterial survival. On the other hand, silencing FBXW7 significantly increases TNF-alpha expression, promoting bacterial elimination. FBXW7 decreases TNF-alpha in a K63-linked ubiquitin signaling dependent manner.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Chen Lin, Yuting Tang, Yuchen Wang, Junli Zhang, Yeyu Li, Shuqin Xu, Bin Xia, Qiran Zhai, Yao Li, Lu Zhang, Jun Liu
Summary: WhiB4 plays a critical role in the disease progression and reactivation of Mycobacterium marinum infection. Targeting WhiB4 may be a promising strategy for the development of novel therapeutics to prevent the reactivation of latent tuberculosis infection.
MICROBIOLOGY SPECTRUM
(2022)
Article
Immunology
Ye-yu Li, Han-Mei Liu, Decheng Wang, Yan Lu, Cairong Ding, Li-Shuang Zhou, Xiang-Yang Wu, Zi-Wei Zhou, Shu-qin Xu, Chen Lin, Lian-Hua Qin, Yao Li, Jun Liu, Hai-Peng Liu, Lu Zhang
Summary: The study found that the AG of Mycobacterium can suppress host immune responses and enhance bacterial intracellular proliferation. The arabinose chains of AG have a greater impact on the virulence and pathogenicity of Mycobacterium.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Yingke Liang, Alicia Plourde, Stephanie A. Bueler, Jun Liu, Peter Brzezinski, Siavash Vahidi, John L. Rubinstein
Summary: Oxidative phosphorylation is a promising target for treating Mycobacterium tuberculosis and other mycobacteria infections. The structure of the mycobacterial electron transport chain reveals the presence of several important components, including the orphan protein MSMEG_2064, acyl phosphati-dylinositol dimannoside, menaquinone, and a purine nucleoside triphosphate. These findings provide insights into the function and structure of the enzyme.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)