Article
Immunology
Davit Baliashvili, Neel R. Gandhi, Soyeon Kim, Michael Hughes, Vidya Mave, Alberto Mendoza-Ticona, Pedro Gonzales, Kim Narunsky, Poongulali Selvamuthu, Sharlaa Badal-Faesen, Caryn Upton, Linda Naini, Elizabeth Smith, Amita Gupta, Gavin Churchyard, Susan Swindells, Anneke Hesseling, N. Sarita Shah
Summary: A multinational study found that at least 10% of household contacts of patients with pulmonary multidrug- or rifampin-resistant tuberculosis are resistant to M. tuberculosis infection, regardless of exposure level. The prevalence of resistance did not significantly differ by sex, age, HIV coinfection, or comorbid conditions. Further research into the genetic or immunologic mechanisms underlying resistance could lead to new therapeutic and vaccine strategies.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Yan Guo, Yuri F. van der Heijden, Fernanda Maruri, Limin Jiang, Robert Morrison, Timothy R. Sterling
Summary: This study marks the first discovery of three RNA editing events in Mycobacterium tuberculosis, providing novel insights into gene expression regulation in this bacterium species.
MICROBIOLOGICAL RESEARCH
(2022)
Article
Immunology
Caroline M. Williams, Abdul K. Muhammad, Basil Sambou, Adama Bojang, Alhaji Jobe, Georgetta K. Daffeh, Olumuyiwa Owolabi, Daniel Pan, Manish Pareek, Michael R. Barer, Jayne S. Sutherland, Pranabashis Haldar
Summary: Mask sampling is a sensitive and noninvasive tool for evaluating the infectiousness of individuals in high tuberculosis (TB) burden settings. It provides better insight into community transmission and can inform public health interventions more reliably than sputum bacillary load.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Mokgerwa Zacharia Monama, Fisayo Olotu, Tzlem Tastan Bishop
Summary: In this study, we investigated the molecular and structural events associated with RIF-resistance in nine clinically reported missense Mtb RNAP mutations. Our findings revealed that these mutations disrupted structural-dynamical attributes and perturbed the RIF-BP, leading to alterations in the active orientation of RIF and loss of essential interactions with the drug. We believe that these findings will significantly contribute to the discovery of new treatment options to overcome antitubercular resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Kyle S. Skalenko, Lingting Li, Yuanchao Zhang, Irina O. Vvedenskaya, Jared T. Winkelman, Alexander L. Cope, Deanne M. Taylor, Premal Shah, Richard H. Ebright, Justin B. Kinney, Yu Zhang, Bryce E. Nickels
Summary: Chemical modifications of RNA 5'-ends allow epitranscriptomic regulation, impacting various aspects of RNA fate. In Escherichia coli cells, RNAs with a 5'-end hydroxyl are produced by primer-dependent transcription initiation using dinucleotide RNAs as primers. The study reveals that primer-dependent initiation in E. coli involves different dinucleotide primers and is influenced by promoter sequences surrounding the primer binding site.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemical Research Methods
Robert A. A. Beagrie, Christoph J. J. Thieme, Carlo Annunziatella, Catherine Baugher, Yingnan Zhang, Markus Schueler, Alexander Kukalev, Rieke Kempfer, Andrea M. M. Chiariello, Simona Bianco, Yichao Li, Trenton Davis, Antonio Scialdone, Lonnie R. R. Welch, Mario Nicodemi, Ana Pombo
Summary: Multiplex-genome architecture mapping (multiplex-GAM) is a faster and more affordable version of genome architecture mapping (GAM), enabling rapid, unbiased, ligation-free mapping of genome-wide chromatin interactions. A detailed comparison of multiplex-GAM and Hi-C using mouse embryonic stem cells reveals that only one-third of the strongest chromatin contacts are shared between the two methods. GAM often detects strong chromatin contacts involving 'active' regions, such as transcribed genes and super-enhancers, while Hi-C more often identifies contacts in 'inactive' regions. This highlights the need for orthogonal advances in genome-wide contact mapping technologies.
Article
Immunology
Maria B. Arriaga, Michael S. Rocha, Betania M. F. Nogueira, Vanessa Nascimento, Mariana Araujo-Pereira, Alexandra B. Souza, Alice M. S. Andrade, Alysson G. Costa, Adriano Gomes-Silva, Elisangela C. Silva, Marina C. Figueiredo, Megan M. Turner, Betina Durovni, Jose R. Lapa-e-Silva, Afranio L. Kritski, Solange Cavalcante, Valeria C. Rolla, Marcelo Cordeiro-Santos, Timothy R. Sterling, Bruno B. Andrade
Summary: This study investigated the epidemiological and clinical characteristics of patients with pulmonary tuberculosis and their close contacts. The results showed that contacts of persons with pulmonary tuberculosis and dysglycemia were at increased risk of being QuantiFERON positive, highlighting the importance of focusing on such close contacts for tuberculosis control.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Microbiology
Qing Sun, Shuqi Wang, Xinlei Liao, Guanglu Jiang, Hairong Huang, Hao Li, Guirong Wang
Summary: Tuberculosis is a leading cause of death worldwide, with the issue of drug-resistant strains. The study found that fidaxomicin has high in vitro activity against Mycobacterium tuberculosis, making it a potential drug to treat Mtb and MDR-TB infections.
JOURNAL OF MEDICAL MICROBIOLOGY
(2021)
Article
Medicine, General & Internal
Cinthya Ruiz-Tagle, Rodrigo Naves, Patricia Garcia, Anna Guenther, Nicole Schneiderhan-Marra, Maria Elvira Balcells
Summary: This study investigated the levels of Mycobacterium tuberculosis (Mtb) specific IgA in saliva at different stages of latent Tuberculosis Infection (TBI). The results showed that the levels of specific IgA were higher in Mtb-infected individuals, but had low discriminatory performance for TBI diagnosis. The study also found the presence of Mtb-specific IgA against multiple antigens in saliva.
FRONTIERS IN MEDICINE
(2023)
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)
Review
Immunology
Shufan Liang, Jiechao Ma, Hanlin Gong, Jun Shao, Jingwei Li, Yuejuan Zhan, Zhoufeng Wang, Chengdi Wang, Weimin Li
Summary: This article reviews the role of noncoding RNAs (ncRNAs) in Mycobacterium tuberculosis infection, highlighting their impact through immune response modulation, and their potential as biomarkers for tuberculosis diagnosis, drug resistance identification, treatment evaluation, and adverse drug reaction prediction.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Liqiang Shen, Giorgio Lai, Linlin You, Jing Shi, Xiaoxian Wu, Maria Puiu, Zhanxi Gu, Yu Feng, Yulia Yuzenkova, Yu Zhang
Summary: This study presents the cryo-EM structures of cyanobacterial transcription initiation complexes, revealing the role of SI3-& sigma; arch interaction in transcription initiation of cyanobacteria. Disruption of this structure affects the growth and stress response of cyanobacteria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Abhishek Mazumder, Richard H. Ebright, Achillefs N. Kapanidis
Summary: This study used single-molecule techniques to investigate the unwinding process of bacterial promoters, and found that the RNAP clamp remains closed during binding to the promoter, continues to stay closed during unwinding, and further closes after unwinding, locking the DNA in the active center cleft of the RNAP.
Article
Microbiology
Shuang Han, Zhen Gong, Tian Liang, Yu Chen, Jianping Xie
Summary: Mycobacterium tuberculosis (Mtb) is a pathogen causing tuberculosis, while Mfd, a bacterial DNA translocase, has functions in resolving transcription replication conflicts, mitigating bacterial damage, and promoting bacteria mutagenesis. There are widespread studies on Mfd in bacteria, but limited research has been done on Mtb.
MICROBIOLOGICAL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Emmanuel Compe, Jean-Marc Egly
Summary: In eukaryotes, transcription of protein-coding genes requires the assembly of a preinitiation machinery at core promoters containing RNAPII and GTFs. Transcription is enhanced by regulatory elements called enhancers, recognized by specific DNA-binding transcription factors. Understanding the transcription initiation mechanism has benefited from the study of altered transcription components associated with human diseases.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Article
Biochemistry & Molecular Biology
Xieyang Guo, Alexander G. Myasnikov, James Chen, Corinne Crucifix, Gabor Papai, Maria Takacs, Patrick Schultz, Albert Weixlbaumer
Article
Multidisciplinary Sciences
Hande Boyaci, James Chen, Rolf Jansen, Seth A. Darst, Elizabeth A. Campbell
Article
Biology
James Chen, Saumya Gopalkrishnan, Courtney Chiu, Albert Y. Chen, Elizabeth A. Campbell, Richard L. Gourse, Wilma Ross, Seth A. Darst
Article
Biochemistry & Molecular Biology
James Chen, Courtney Chiu, Saumya Gopalkrishnan, Albert Y. Chen, Paul Dominic B. Olinares, Ruth M. Saecker, Jared T. Winkelman, Michael F. Maloney, Brian T. Chait, Wilma Ross, Richard L. Gourse, Elizabeth A. Campbell, Seth A. Darst
Article
Biochemistry & Molecular Biology
James Chen, Brandon Malone, Eliza Llewellyn, Michael Grasso, Patrick M. M. Shelton, Paul Dominic B. Olinares, Kashyap Maruthi, Edward T. Eng, Hasan Vatandaslar, Brian T. Chait, Tarun M. Kapoor, Seth A. Darst, Elizabeth A. Campbell
Article
Multidisciplinary Sciences
Mirjana Lilic, James Chen, Hande Boyaci, Nathaniel Braffman, Elizabeth A. Hubin, Jennifer Herrmann, Rolf Mueller, Rachel Mooney, Robert Landick, Seth A. Darst, Elizabeth A. Campbell
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
Paul Dominic B. Olinares, Jin Young Kang, Eliza Llewellyn, Courtney Chiu, James Chen, Brandon Malone, Ruth M. Saecker, Elizabeth A. Campbell, Seth A. Darst, Brian T. Chait
Summary: Recent advancements in single-particle cryogenic electron microscopy have allowed for high-resolution structural determination of protein assemblies, although the method remains time-consuming and resource-intensive. The development of a native mass spectrometry platform provides rapid sample quality assessment and streamlined screening before lengthy cryo-EM analyses, enhancing research efficiency.
Article
Multidisciplinary Sciences
Brandon Malone, James Chen, Qi Wang, Eliza Llewellyn, Young Joo Choi, Paul Dominic B. Olinares, Xinyun Cao, Carolina Hernandez, Edward T. Eng, Brian T. Chait, David E. Shaw, Robert Landick, Seth A. Darst, Elizabeth A. Campbell
Summary: Backtracking, a common regulatory feature in transcription, is found in viruses as well, with evidence suggesting that SARS-CoV-2 RdRp may utilize backtracking for viral transcription and replication. The interaction between RdRp and nsp13 helicase facilitates backtracking, which may aid in proofreading and antiviral resistance for SARS-CoV-2.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
James Chen, Qi Wang, Brandon Malone, Eliza Llewellyn, Yakov Pechersky, Kashyap Maruthi, Ed T. Eng, Jason K. Perry, Elizabeth A. Campbell, David E. Shaw, Seth A. Darst
Summary: In the complex of SARS-CoV-2 nsp13 helicase and RNA polymerase, a mechanism has been revealed through cryo-EM and MD simulations that controls their movement in opposite directions on RNA. This mechanism allows the helicase to drive the polymerase backward on the RNA template and switch between RNA synthesis and backtracking.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Andreas U. Mueller, James Chen, Mengyu Wu, Courtney Chiu, B. Tracy Nixon, Elizabeth A. Campbell, Seth A. Darst
Summary: Bacterial transcription initiation requires s factors to induce transcription bubble formation. The canonical s factor sigma(70) enables DNA melting and formation of the transcription bubble by recognizing conserved bases of the promoter -10 motif. However, the mechanism of transcription bubble formation and nucleation during sigma(N)-mediated transcription initiation is still poorly understood. This study shows that sigma(N) captures a flipped, unstacked base between its N-terminal region I (RI) and extra-long helix features, similar to sigma(70). The RI then inserts into the nascent bubble to stabilize it before engagement of the ATPase activator.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Editorial Material
Biochemistry & Molecular Biology
James Chen, Damian C. Ekiert
Summary: This paragraph describes a drug for treating multidrug-resistant tuberculosis, which targets the key enzyme ATP synthase in cellular respiration. A recent study shows that this drug, along with another inhibitor, prevents the enzymatic function by inhibiting the necessary rotational motions.
Article
Multidisciplinary Sciences
James Chen, Alice Fruhauf, Catherine Fan, Jackeline Ponce, Beatrix Ueberheide, Gira Bhabha, Damian C. Ekiert
Summary: To cause tuberculosis, Mycobacterium tuberculosis needs to obtain nutrients from the host cells. The MCE proteins, encoded by gene clusters, play a crucial role in the virulence of M. tuberculosis by transporting fatty acids and cholesterol across the impermeable mycobacterial cell envelope. This study reveals the cryo-EM structure of the Mce1 lipid-import machine in Mycobacterium smegmatis and provides insights into the mechanism of lipid transport across the mycobacterial cell envelope.
Article
Biochemistry & Molecular Biology
Leila T. Alexander, Janani Durairaj, Andriy Kryshtafovych, Luciano A. Abriata, Yusupha Bayo, Gira Bhabha, Cecile Breyton, Simon G. Caulton, James Chen, Seraphine Degroux, Damian C. Ekiert, Benedikte S. Erlandsen, Peter L. Freddolino, Dominic Gilzer, Chris Greening, Jonathan M. Grimes, Rhys Grinter, Manickam Gurusaran, Marcus D. Hartmann, Charlie J. Hitchman, Jeremy R. Keown, Ashleigh Kropp, Petri Kursula, Andrew L. Lovering, Bruno Lemaitre, Andrea Lia, Shiheng Liu, Maria Logotheti, Shuze Lu, Sigurbjorn Markusson, Mitchell D. Miller, George Minasov, Hartmut H. Niemann, Felipe Opazo, George N. N. Phillips Jr, Owen R. Davies, Samuel Rommelaere, Monica Rosas-Lemus, Pietro Roversi, Karla Satchell, Nathan Smith, Mark A. Wilson, Kuan-Lin Wu, Xian Xia, Han Xiao, Wenhua Zhang, Z. Hong Zhou, Krzysztof Fidelis, Maya Topf, John Moult, Torsten Schwede
Summary: We conducted a thorough analysis of selected CASP15 targets, focusing on their biological and functional significance. The authors of the structures identified and discussed key protein features and evaluated the accuracy of the submitted predictions. While the overall ability to predict protein structures is impressive, reproducing uncommon features remains challenging. The need for novel scoring strategies to emphasize biologically relevant structural regions is highlighted, particularly when dealing with conformational flexibility and large multimeric complexes. Integration of computational and experimental techniques will play a crucial role in unraveling future challenges in structural molecular biology.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Review
Microbiology
James Chen, Hande Boyaci, Elizabeth A. Campbell
Summary: This review examines universal pathways and diverse regulatory mechanisms in transcription initiation in evolutionarily divergent bacteria, as well as the mechanisms by which antimicrobials inhibit transcription initiation. The study highlights the simplicity of mechanistic studies in transcription initiation in bacteria and the importance of bacteria in human health.
NATURE REVIEWS MICROBIOLOGY
(2021)
