Article
Microbiology
Cara Adolph, Matthew B. McNeil, Gregory M. Cook
Summary: New drugs are urgently needed to combat tuberculosis. This study provides insight into the importance of succinate oxidation in Mycobacterium tuberculosis and the consequences of inhibiting this process. Additionally, the study shows that impaired succinate oxidation affects the activity of anti-tuberculosis drugs. These findings are valuable for the development of bioenergetic inhibitors.
Article
Biochemistry & Molecular Biology
Marta Alberti, Stefano Sainas, Erika Ronchi, Marco L. Lolli, Donatella Boschi, Menico Rizzi, Davide M. Ferraris, Riccardo Miggiano
Summary: Researchers have characterized the full-length MTB DHODH and discovered the first selective inhibitor. This study has significant implications for drug treatment of tuberculosis.
Article
Multidisciplinary Sciences
Vadim Nikitushkin, Margarita Shleeva, Dmitry Loginov, F. Filip Dycka, Jan Sterba, Arseny Kaprelyants
Summary: This study investigates the proteins accumulated in dormant Mycobacterium tuberculosis cells using proteomic profiling and reveals significant differences in proteins compared to actively growing cells, as well as pathways related to dormancy adaptation. These findings contribute to a better understanding of the metabolic processes in dormant tuberculosis and have the potential to lead to the discovery of immunodiagnostic tests and effective drugs for latent tuberculosis.
Article
Biochemistry & Molecular Biology
Saif Khan, Mahvish Khan, Mohtashim Lohani, Saheem Ahmad, Subuhi Sherwani, Sundeep Bhagwath, Mohd Wajid A. Khan, Mohd Wahid, Farrukh Aqil, Shafiul Haque
Summary: This study investigated the unfolding of Mycobacterium Aspartate beta semialdehyde dehydrogenase (ASADH) using spectroscopic techniques and size exclusion chromatography. The unfolding of the apo ASADH was found to be non-cooperative, while the unfolding of the holoenzyme was cooperative. The presence of NADP/H stabilizes the tryptophan environment and the native NADP/H-bound enzyme. The folded holoenzyme was shown to be conformationally more stable compared to the apo state. These findings are important for the discovery of novel drugs targeting ASADH.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Immunology
David Salcines-Cuevas, Hector Teran-Navarro, Ricardo Calderon-Gonzalez, Paula Torres-Rodriguez, Raquel Tobes, Manuel Fresno, Jorge Calvo-Montes, I. Concepcion Perez Del Molino-Bernal, Sonsoles Yanez-Diaz, Carmen Alvarez-Dominguez
Summary: The N-terminal 22 amino acid peptides of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are highly homologous among pathogenic bacteria like Listeria, Mycobacterium, and Streptococcus, making them ideal candidates for universal vaccine designs. Vaccines containing these peptides demonstrated high immunogenicity, lack of toxicity, and cross-protection immunity in mouse models infected with different pathogens.
Article
Immunology
Xiao Wang, Ruifang Yang, Sihan Liu, Yan Guan, Chunling Xiao, Chuanyou Li, Jianzhou Meng, Yu Pang, Yishuang Liu
Summary: The study showed that IMB-XMA0038 is an inhibitor of MtASADH and can effectively inhibit the growth of drug-resistant MTB strains with minimal cytotoxicity in vitro and in vivo. In a mouse model, IMB-XMA0038 reduced the MTB colony forming units in the lung by 1.67 log10 at a dose of 25 mg/kg for 15 days, demonstrating its promising potential as a lead compound against drug-resistant tuberculosis.
EMERGING MICROBES & INFECTIONS
(2021)
Article
Multidisciplinary Sciences
Alexandre Gouzy, Claire Healy, Katherine A. Black, Kyu Y. Rhee, Sabine Ehrt
Summary: In acidic pH conditions, Mycobacterium tuberculosis adapts its metabolism to preferentially assimilate lipids, like oleic acid, over carbohydrates. Lack of certain enzymes necessary for lipid assimilation can be lethal to M. tuberculosis under acidic conditions, highlighting the pathogen's ability to alter its carbon diet in response to pH stress.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Immunology
Cheldon Ann Alcantara, Ira Glassman, Kevin H. Nguyen, Arpitha Parthasarathy, Vishwanath Venketaraman
Summary: Mycobacterium tuberculosis (M. tb) remains a major cause of death in developing countries. The BCG vaccine is widely used in developing countries but its efficacy is still uncertain. Neutrophils play a crucial role in the immune response against M. tb, promoting clearance of the bacteria and regulating the inflammatory response. This review highlights the role of neutrophils during M. tb infection and emphasizes the need for more research on effective vaccination.
Article
Biochemistry & Molecular Biology
Wanggang Tang, Chuanyue Gui, Tingting Zhang
Summary: In this study, we successfully optimized the expression of the Mycobacterium tuberculosis Rv0439c enzyme and found that it has a preference for NADP(+) and may play a role in retinol metabolism. These findings provide a basis for future functional and structural studies of Rv0439c, contributing to a better understanding of Mtb biology.
MOLECULAR BIOTECHNOLOGY
(2023)
Article
Immunology
Mariana Herrera, Yoav Keynan, Lucelly Lopez, Diana Marin, Lazaro Velez, Paul J. McLaren, Zulma Vanessa Rueda
Summary: We studied the immune changes in newly acquired tuberculosis infection in a population deprived of liberty in Colombian prisons. We found differences in immune levels between individuals with new tuberculosis infection and those incarcerated for short and long periods of time. Certain cytokines/chemokines were associated with new tuberculosis infection and tuberculosis disease.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Stephanie Fischinger, Deniz Cizmeci, Sally Shin, Leela Davies, Patricia S. Grace, Aida Sivro, Nonhlanhla Yende-Zuma, Hendrik Streeck, Sarah M. Fortune, Douglas A. Lauffenburger, Kogieleum Naidoo, Galit Alter
Summary: South Africa has the highest prevalence of HIV and tuberculosis co-infection globally, with HIV infected individuals having a greater likelihood of developing recurrent TB. This study investigated the humoral response in HIV co-infected individuals with and without recurrent TB, finding differences in antibody profiles, particularly decreased Mtb-antigen specific IgG3 titers in individuals with recurrent TB. These findings suggest a potential role for Mtb-specific IgG3 responses as biomarkers or mediators of protective immunity against Mtb recurrence.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemical Research Methods
Paula J. Gomez-Gonzalez, Susana Campino, Jody E. Phelan, Taane G. Clark
Summary: This study compared the genome sequencing of clinical isolates of Mycobacterium tuberculosis using Oxford Nanopore Technologies (ONT) sequencing and Illumina HiSeq sequencing. The analysis showed that ONT sequencing is robust for detecting single nucleotide polymorphisms and provides improved coverage in repetitive regions. It also demonstrated high concordance in variants associated with drug resistance. ONT sequencing is a promising tool for tuberculosis genomic investigations and can inform clinical and surveillance decision-making to reduce the disease burden.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Immunology
Shuping Li, Xiaohua Wang, Yuming Zhao, Juan Yang, Tianjiao Cui, Zhizhuang Joe Zhao, Yun Chen, Zhihua Zheng
Summary: The PTPN22-C1858T polymorphism is not significantly associated with higher susceptibility to M. tuberculosis infection in Caucasians and Asians, but is relevant to increased susceptibility to M. leprae infection. Further well-designed studies with sufficient populations are required to verify these conclusions.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Hector Teran-Navarro, David Salcines-Cuevas, Ricardo Calderon-Gonzalez, Raquel Tobes, Jorge Calvo-Montes, Inmaculada Concepcion Perez-Del Molino Bernal, Sonsoles Yanez-Diaz, Manuel Fresno, Carmen Alvarez-Dominguez
Summary: It has been shown that using DC loaded with LM-GAPDH recombinant proteins as vaccine vectors is the safest and most immunogenic choice, providing effective protection against Listeria, Mycobacterium, and Streptococcus groups in adult vaccination.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Nan Wang, Yongliang Yao, Yingfen Qian, Dewen Qiu, Hui Cao, Huayuan Xiang, Jianjun Wang
Summary: Exosomes are double-membrane vesicles containing various lipids, proteins, mRNAs, and non-coding RNAs, and are involved in multiple physiological processes such as intercellular communication and immunomodulation. Studies have found that the components of exosomes released from host cells are altered following Mycobacterium tuberculosis infection. The contents of exosomes provide excellent biomarkers for the diagnosis, efficacy evaluation, and prognosis of tuberculosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Medicinal
Hajjaj H. M. Abdu-Allah, Bahaa G. M. Youssif, Mostafa H. Abdelrahman, Mohammed K. Abdel-Hamid, Rudraraju Srilakshmi Reshma, Perumal Yogeeswari, Tarek Aboul-Fadl, Dharmarajan Sriram
ARCHIVES OF PHARMACAL RESEARCH
(2017)
Article
Chemistry, Medicinal
Variam U. Jeankumar, Shalini Saxena, Rahul Vats, Rudraraju Srilakshmi Reshma, Renuka Janupally, Pushkar Kulkarni, Perumal Yogeeswari, Dharmarajan Sriram
Article
Chemistry, Medicinal
Variam Ullas Jeankumar, Rudraraju Srilakshmi Reshma, Rahul Vats, Renuka Janupally, Shalini Saxena, Perumal Yogeeswari, Dharmarajan Sriram
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Katharina Brunner, Selma Maric, Rudraraju Srilakshmi Reshma, Helena Almqvist, Brinton Seashore-Ludlow, Anna-Lena Gustavsson, Omer Poyraz, Perumal Yogeeswari, Thomas Lundback, Michaela Vallin, Dharmarajan Sriram, Robert Schnell, Gunter Schneider
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Prasanthi Malapati, Vagolu Siva Krishna, Radhika Nallangi, Nikhila Meda, Rudraraju Reshma Srilakshmi, Dharmarajan Sriram
BIOORGANIC & MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Sandeep Kumar Marvadi, Vagolu Siva Krishna, Goverdhan Surineni, Rudraraju Srilakshmi Reshma, Balasubramanian Sridhar, Dharmarajan Sriram, Srinivas Kantevari
BIOORGANIC CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Peter Vella, Reshma Srilakshmi Rudraraju, Thomas Lundback, Hanna Axelsson, Helena Almqvist, Michaela Vallin, Gunter Schneider, Robert Schnell
Summary: The spread of antibiotic resistance within the ESKAPE group of human pathogenic bacteria poses challenges in treatment, motivating efforts to validate FabG enzymes as potential targets for antibiotic development. Small-molecule screening identified mu M inhibitors that bind at an allosteric site in the FabG structure, potentially interfering with fatty acid biosynthesis in clinically relevant ESKAPE pathogens.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Karen Schriever, Patricia Saenz-Mendez, Reshma Srilakshmi Rudraraju, Natalie M. Hendrikse, Elton P. Hudson, Antonino Biundo, Robert Schnell, Per-Olof Syren
Summary: Structural information is essential for understanding catalytic mechanisms and guiding enzyme engineering efforts. By engineering thermostable ancestral enzymes, reliable homology models of extant biocatalysts can be accessed. This study demonstrates the versatility of ancestral sequence reconstruction combined with enzyme engineering as a valuable tool in chemical biology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Medicinal
Saiprasad Dasugari Varakala, Rudraraju Srilakshmi Reshma, Robert Schnell, Sriram Dharmarajan
Summary: This study focuses on the lead expansion of two hit molecules, resulting in the discovery of 43 analogues. Compounds 15 and 19 exhibit broad-spectrum inhibition activity against FabG.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Immunology
Reshma S. Rudraraju, Samer S. Daher, Ricardo Gallardo-Macias, Xin Wang, Matthew B. Neiditch, Joel S. Freundlich
Summary: This review summarizes the current research progress on the druggable target KasA in Mycobacterium tuberculosis, focusing on structure-based design methods using X-ray crystal structures. The discussed inhibitor classes and their interactions with KasA provide insights into the development of new KasA inhibitors for studying the basic biology of M. tuberculosis and combating drug-sensitive and drug-resistant infections.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Chemistry, Medicinal
Katharina Brunner, Eva Maria Steiner, Rudraraju Srilakshmi Reshma, Dharmarajan Sriram, Robert Schnell, Gunter Schneider
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2017)
Article
Chemistry, Medicinal
Shinde Vidyacharan, Chandan Adhikari, Vagolu Siva Krishna, Rudraraju Srilakshmi Reshma, Dharmarajan Sriram, Duddu S. Sharada
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2017)