Article
Biochemistry & Molecular Biology
Sunita, Nirjara Singhvi, Vipin Gupta, Yogendra Singh, Pratyoosh Shukla
Summary: Implementation of computational tools in identifying drug targets for Tuberculosis has shown promise. Nucleoid-Associated Proteins have been found to play a significant role in regulating cellular processes of Mycobacterium tuberculosis, making them potential targets for new drugs. This study used computational methods to identify potential inhibitors for eight Nucleoid-Associated Proteins, and found several FDA-approved drugs as novel targets with therapeutic potential for TB.
MOLECULAR BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Peipei Zhang, Xiaohui Zhao, Yawen Wang, Ke Du, Zhihao Wang, Jianfeng Yu, Gang Chang, Steve Matthews, Hongliang Wang, Bing Liu
Summary: The HU protein is crucial for bacterial cell viability and serves as an antibiotic target. This study reveals that Gp46 from bacteriophage SPO1 can inhibit HU, leading to growth defects in bacteria. Through structural analysis, it is found that Gp46 occupies the DNA binding site of HU, thus preventing DNA binding. This discovery provides valuable insights into developing antibacterial and anti-malaria drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Pavla Stojkova, Petra Spidlova
Summary: HU protein, a member of the nucleoid-associated protein family, plays a crucial role in regulating bacterial virulence, pathogenesis, and survival. Recent studies suggest that HU protein may not only exist inside bacteria but also be secreted outside bacteria and even enter host cells. However, its specific role in host cells is still not well understood and further research is needed.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Chinmay Anand, Meghna Santoshi, Prakruti R. Singh, Valakunja Nagaraja
Summary: The research focused on the nucleoid-associated protein MtHU in Mycobacterium tuberculosis, identifying a succinyltransferase Rv0802c that interacts with and succinylates MtHU. The succinylation of MtHU affects its binding to DNA, but in vivo expression of Rv0802c does not significantly alter the nucleoid architecture.
Review
Chemistry, Medicinal
Milan Urban, Veronika Slachtova, Lucie Brulikova
Summary: Mycobacterial energy metabolism, particularly the oxidative phosphorylation pathway, has become increasingly important as a molecular target for the development of new anti-TB drugs. Small organic molecules targeting this pathway have shown promising activity against latent and resistant TB strains, with FDA-approved inhibitors confirming the value of targeting mycobacterial energy metabolism.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Microbiology
Kasi Viswanatharaju Ruddraraju, Devesh Aggarwal, Zhong-Yin Zhang
Summary: Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis, and the treatment of drug-resistant TB requires therapeutic agents with novel mechanisms. Antivirulence, focusing on bacterial virulence factors, is an alternative strategy for treating diseases. Recent advances in understanding the roles of mPTPA and mPTPB in the pathogenesis of TB have been made, along with the discovery of potent, selective, and well-characterized small molecule inhibitors for these proteins in the past decade.
Article
Biochemistry & Molecular Biology
Kanika Arora, Bhishem Thakur, Archit Gupta, Purnananda Guptasarma
Summary: In enteric bacteria like Escherichia coli, there are two homologs of the DNA-binding nucleoid associated protein (NAP) known as HU, which exist in different forms and dominate different stages of bacterial growth. Due to similarities in their properties and the difficulty in purifying them separately, these dimeric forms can interfere with each other. The creation of a functional analog of HU-AB, termed HU-B-A, solves this problem by combining HU-B and HU-A chains into a single polypeptide with a higher stability and dominance in mixtures.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Editorial Material
Microbiology
Frederic D. Schramm, Heath Murray
Summary: In this study, it was found that Bacillus subtilis HU (HBsu) plays a crucial role in driving DnaA-dependent initiation of DNA replication at the chromosome origin, revealing the importance of HU in replication initiation and other cellular functions.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Mona M. Katariya, Matthew Snee, Richard B. Tunnicliffe, Madeline E. Kavanagh, Helena I. M. Boshoff, Cecilia N. Amadi, Colin W. Levy, Andrew W. Munro, Chris Abell, David Leys, Anthony G. Coyne, Kirsty J. McLean
Summary: Mycobacterium tuberculosis (Mtb) caused approximately 1.6 million deaths in 2021. Due to the emergence of drug resistance, there is an urgent need for new therapeutic agents and ongoing drug discovery efforts. Host-derived lipids like cholesterol not only support Mtb growth but also play a role in immunomodulation and immune evasion. Mtb cytochrome P450 (CYP) enzymes, particularly CYP125 and CYP142, are potential targets for inhibition in lipid catabolism. Compounds based on an ethyl 5-(pyridin-4-yl)-1H-indole-2-carboxylate pharmacophore showed strong binding to both CYP125 and CYP142, with in-cell activity against drug-resistant isolates. These findings are important for developing additional treatment options and exploring the role of CYP125 and CYP142 in Mtb pathogenesis.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Chemistry, Medicinal
Fei Xia, Haoling Zhang, Huanaoyu Yang, Mingming Zheng, Wenjian Min, Chengliang Sun, Kai Yuan, Peng Yang
Summary: Tuberculosis (TB) is a major threat to humans, but the current drug treatment strategy is insufficient. This review focuses on the targeting mechanism of Pks13 for TB treatment and summarizes recent advances in Pks13 inhibitors, including the challenges faced during their discovery and the rational design strategies employed to overcome these obstacles, which could aid the development of novel Pks13 inhibitors in the future.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Cell Biology
Eliza Kramarska, Flavia Squeglia, Flavio De Maio, Giovanni Delogu, Rita Berisio
Summary: PE_PGRS proteins are surface antigens of Mycobacterium tuberculosis and can interact with host receptors. Understanding the structure of PE_PGRS33, particularly its PGRS domain, may lead to new vaccination strategies against TB. By targeting specific features of the PGRS domain, such as exposed PGII sandwiches, a humoral response could be induced for potential vaccine development.
Article
Biochemistry & Molecular Biology
Dafeng Liu, Cai Yuan, Chenyun Guo, Mingdong Huang, Donghai Lin
Summary: This study reported the crystal structure and functional mechanism of the CpsY protein in Mycobacterium tuberculosis. The researchers found that CpsY has conserved regions and spacer segments surrounding its catalytic cavity, and the residue R419 is strictly conserved in regulating its phosphotransferase activity. In addition, deletion of certain spacer segments drastically increased the enzyme activity of CpsY.
Article
Biochemistry & Molecular Biology
Annabel Itterbeek, Amber Possemiers, Yunus Colak, Leonard E. Backer, Abram Aertsen, Rob Lavigne, Jan Paeshuyse
Summary: This study screened Mycophage endolysins and identified CBDs with affinity to Mycobacterium bovis. The secondary structure analysis revealed the presence of potential new CBDs in other endolysins. Fusion proteins containing these CBDs were constructed and shown to have affinity to Mycobacterium bovis. Furthermore, two CBDs were able to fluorescently label Mycobacterium bovis in milk samples.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Hongjuan Zhang, Ying Chen, Yu Zhang, Luyao Qiao, Xiangyin Chi, Yanxing Han, Yuan Lin, Shuyi Si, Jiandong Jiang
Summary: Tuberculosis is a deadly disease caused by Mycobacterium tuberculosis, and finding new drugs to combat it is urgently needed. The FtsZ/SepF interaction has been identified as a promising target for anti-TB drugs, and a compound named T0349 has been discovered to inhibit this interaction and prevent bacterial cell division.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Microbiology
Chao Du, Joost Willemse, Amanda M. Erkelens, Victor J. Carrion, Remus T. Dame, Gilles P. van Wezel
Summary: This study identified a novel nucleoid-associated protein (NAP), Gbn, in Actinobacteria that binds to GATC sequences and plays a significant role in the growth and development of Streptomyces. Gbn has broad effects on global gene expression during the late developmental stage.
Article
Immunology
Dong Eun Kim, Maria-Giuseppina Procopio, Soumitra Ghosh, Seung-Hee Jo, Sandro Goruppi, Francesco Magliozzi, Pino Bordignon, Victor Neel, Paolo Angelino, G. Paolo Dotto
JOURNAL OF EXPERIMENTAL MEDICINE
(2017)
Article
Biochemistry & Molecular Biology
Harshavardhan Khare, Debayan Dey, Chilakapati Madhu, Dillip Senapati, Srinivasarao Raghothama, Thimmaiah Govindaraju, Suryanarayanarao Ramakumar
MOLECULAR BIOSYSTEMS
(2017)
Article
Biochemistry & Molecular Biology
Debayan Dey, Valakunja Nagaraja, Suryanarayanarao Ramakumar
MOLECULAR PHYLOGENETICS AND EVOLUTION
(2017)
Article
Medicine, Research & Experimental
Andrea Clocchiatti, Soumitra Ghosh, Maria-Giuseppina Procopio, Luigi Mazzeo, Pino Bordignon, Paola Ostano, Sandro Goruppi, Giulia Bottoni, Atul Katarkar, Mitchell Levesque, Peter Koelblinger, Reinhard Dummer, Victor Neel, Berna C. Ozdemir, G. Paolo Dotto
JOURNAL OF CLINICAL INVESTIGATION
(2018)
Article
Biochemistry & Molecular Biology
Chandreyee Datta, Rajiv Kumar Jha, Wareed Ahmed, Sohini Ganguly, Soumitra Ghosh, Valakunja Nagaraja
MOLECULAR MICROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Meisam Nosrati, Debayan Dey, Atousa Mehrani, Sarah E. Strassler, Natalia Zelinskaya, Eric D. Hoffer, Scott M. Stagg, Christine M. Dunham, Graeme L. Conn
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Emily G. Kuiper, Debayan Dey, Paige A. LaMore, Joshua P. Owings, Samantha M. Prezioso, Joanna B. Goldberg, Graeme L. Conn
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Giulia Bottoni, Atul Katarkar, Beatrice Tassone, Soumitra Ghosh, Andrea Clocchiatti, Sandro Goruppi, Pino Bordignon, Paris Jafari, Fabio Tordini, Thomas Lunardi, Wolfram Hoetzenecker, Victor Neel, Joachim Lingner, G. Paolo Dotto
NATURE COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
James T. Taylor, Prasun K. Mukherjee, Lorraine S. Puckhaber, Karuna Dixit, Tatyana I. Igumenova, Charles Suh, Benjamin A. Horwitz, Charles M. Kenerley
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2020)
Article
Microbiology
Ashley R. Cross, Vishnu Raghuram, Zihuan Wang, Debayan Dey, Joanna B. Goldberg
JOURNAL OF BACTERIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Karuna Dixit, N. Megha Karanth, Smita Nair, Khushboo Kumari, Kalyan S. Chakrabarti, Handanahal S. Savithri, Siddhartha P. Sarma
Article
Immunology
Andrew S. Mendiola, Zhaoqi Yan, Karuna Dixit, Jeffrey R. Johnson, Mehdi Bouhaddou, Anke Meyer-Franke, Min-Gyoung Shin, Yu Yong, Ayushi Agrawal, Eilidh MacDonald, Gayathri Muthukumar, Clairice Pearce, Nikhita Arun, Belinda Cabriga, Rosa Meza-Acevedo, Maria del Pilar S. Alzamora, Scott S. Zamvil, Alexander R. Pico, Jae Kyu Ryu, Nevan J. Krogan, Katerina Akassoglou
Summary: Akassoglou and colleagues used single-cell RNA sequencing and phosphoprotein analysis to study the responses of CNS microglia and macrophages to blood proteins. They found that microglia activation by immune and vascular signals could be potential therapeutic targets. It is still largely unknown how blood proteins polarize innate immune cells.
Review
Biochemistry & Molecular Biology
Learnmore Jeremia, Benjamin E. Deprez, Debayan Dey, Graeme L. Conn, William M. Wuest
Summary: The rise of multidrug-resistant bacterial infections is a global concern. Pathogen associated resistance-conferring ribosomal RNA (rRNA) methyltransferases are increasingly spreading among human pathogens and could contribute significantly to the increased likelihood of a post-antibiotic era. This article summarizes their prevalence, the fitness cost(s) to bacteria of their acquisition and expression, and current efforts toward targeting clinically relevant enzymes of this class to stimulate future studies.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Min Ma, Soumitra Ghosh, Daniele Tavernari, Atul Katarkar, Andrea Clocchiatti, Luigi Mazzeo, Anastasia Samarkina, Justine Epiney, Yi-Ru Yu, Ping-Chih Ho, Mitchell P. Levesque, Berna C. Ozdemir, Giovanni Ciriello, Reinhard Dummer, G. Paolo Dotto
Summary: The susceptibility to melanoma differs significantly between male and female populations, with androgen receptor (AR) levels in melanocytes playing a role in disease progression. Modulation of AR activity affects melanoma cell proliferation and senescence, with downstream effects on gene expression related to survival pathways. Targeting AR shows promise in suppressing melanomagenesis and enhancing immune responses in melanoma treatment.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Chinmay Anand, Rajni Garg, Soumitra Ghosh, Valakunja Nagaraja
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2017)