Article
Biochemistry & Molecular Biology
Ritesh R. Sevalkar, Joel N. Glasgow, Martin Pettinati, Marcelo A. Marti, Vineel P. Reddy, Swati Basu, Elmira Alipour, Daniel B. Kim-Shapiro, Dario A. Estrin, Jack R. Lancaster, Adrie J. C. Steyn
Summary: This study reveals that Mycobacterium tuberculosis can sense and respond to hydrogen sulfide (H2S) signal via the DosS/T/R system. The binding of H2S to DosS heme iron increases DosS autokinase activity and subsequent phosphorylation of DosR, leading to the modulation of gene expression. These findings demonstrate a novel mechanism for Mtb to sense and respond to H2S and highlight the remarkable plasticity of DosS.
Article
Immunology
Parul Bhatt, Monika Sharma, Prem Prakash Sharma, Brijesh Rathi, Sadhna Sharma
Summary: This study confirms the adjuvant activity of Rv2627c and Rv2628 proteins as toll-like receptor agonists. Through in-vitro experiments, it has been demonstrated that these proteins can increase the expression of TLR2, TLR4, and co-stimulatory molecules, and activate downstream signaling molecules and pro-inflammatory cytokines in macrophages. The stable interaction between Rv2627c/Rv2628 and TLR2/TLR4 has been confirmed through molecular docking and simulations. The adjuvant activity of Rv2628 has been further validated using a protein adjuvanted vaccine construct.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Chemistry, Physical
Deeksha Sharma, Saurabh Sharma, Niharika Sinha, Neha Jain, Amit Kumar, Anjana Sarkar, Jaya Sivaswami Tyagi, Rajesh Kumar Gupta
Summary: This study reported a high throughput screening assay to identify inhibitors that specifically target DevR and successfully discovered novel inhibitors. The interaction between these inhibitors and DevR was experimentally confirmed. These findings provide a new and promising scaffold for designing anti-DevR molecules to intercept mycobacterial dormancy.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
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
Chemistry, Medicinal
Priyanka Chauhan, Ishara Datta, Abhijeet Dhiman, Uma Shankar, Amit Kumar, Atul Vashist, Tarun Kumar Sharma, Jaya Sivaswami Tyagi
Summary: Tuberculosis is a major public health threat globally, and targeting the DevR-DevS two-component system has emerged as a potential approach for drug development. In this study, researchers used an in vitro evolution approach to develop a panel of DNA aptamers that interact with the DevR protein in Mycobacterium tuberculosis. The best-performing aptamer, APT-6, was found to inhibit the transcription activity of DevR and offers potential for developing novel therapeutic strategies against tuberculosis.
ACS INFECTIOUS DISEASES
(2022)
Article
Infectious Diseases
Mohd Shiraz, Surabhi Lata, Pankaj Kumar, Umate Nachiket Shankar, Mohd Akif
Summary: Immunoinformatics methods were used to predict promiscuous antigenic T-cell epitopes from putative nitro-reductases of the DosR regulon for the design of a potential vaccine against latent tuberculosis. The predicted epitopes may aid in developing a subunit vaccine against latent TB, which can be administered alongside BCG to enhance efficacy.
INFECTION GENETICS AND EVOLUTION
(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)
Review
Immunology
Li Wei, Kai Liu, Qingzhi Jia, Hui Zhang, Qingli Bie, Bin Zhang
Summary: Tuberculosis caused by Mycobacterium tuberculosis remains a major health issue, as the bacteria can replicate and persist in host cells. Noncoding RNAs (ncRNAs) play critical roles in regulating the host response against Mycobacterium tuberculosis infection, with potential clinical implications for tuberculosis diagnosis and therapy development.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Infectious Diseases
Lirong Mao, Lifa Xu, Xiaochun Wang, Jianpeng Du, Qishan Sun, Zilun Shi, Jian Wang, Yingru Xing, Yixing Su, Ying Xu, Zhiyang Qi, Lu Xia, Jilei Ma, Jingyan Zhang
Summary: DosR antigens and Rpfs play important roles in the diagnosis of tuberculosis at different stages, but their diagnostic effectiveness is limited in active tuberculosis infections. DosR antigens are more immunogenic than Rpfs in latent tuberculosis infections, while the opposite is true in relapse tuberculosis infections. Specifically, Rv2003c is the best antigen for diagnosing latent tuberculosis infections, while Rv0867c is the best antigen for identifying relapse tuberculosis infections.
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
(2022)
Review
Microbiology
Manikuntala Kundu, Joyoti Basu
Summary: Mycobacterium tuberculosis can survive in its host for extended periods, remaining dormant within granulomas. Understanding the mechanisms of entry into and exit from dormancy is crucial for developing new tuberculosis treatment strategies. Transcriptomic and proteomic approaches have revealed key genes and pathways involved in dormancy and reactivation of M. tuberculosis.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Microbiology
Elena G. Salina, Vadim Makarov
Summary: Both latent and active TB infections are caused by a heterogeneous population of mycobacteria, and understanding the mechanisms underlying dormant and resuscitation phases of M. tuberculosis can help control latent infection and prevent transmission.
Article
Multidisciplinary Sciences
Barbara Tizzano, Tobias K. Dallenga, Christian Utpatel, Jochen Behrends, Susanne Homolka, Thomas A. Kohl, Stefan Niemann
Summary: The study reveals that survival and recovery from oxygen starvation in different strains of Mycobacterium tuberculosis are lineage-dependent, with strains belonging to the Euro-American lineage (L4) demonstrating similar survival and resuscitation characteristics, while strains from other lineages show varied responses to oxygen starvation. The findings suggest that resuscitation after oxygen starvation is not a universal feature of all M. tuberculosis strains.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Kala Jyothi Kanaparthi, Sumbul Afroz, Gillipsie Minhas, Anurupa Moitra, Rafiq Ahmad Khan, Jayashankar Medikonda, Saima Naz, Sai Nikhith Cholleti, Sharmistha Banerjee, Nooruddin Khan
Summary: The study revealed the importance of DosR protein Rv0569 in initiating Th1 immune responses, suggesting its potential as a vaccine candidate against latent tuberculosis infection.
IMMUNOLOGY LETTERS
(2022)
Review
Immunology
Akanksha Verma, Antara Ghoshal, Ved Prakash Dwivedi, Ashima Bhaskar
Summary: Mycobacterium tuberculosis is an intracellular pathogen that induces dormancy, counteracting host stress responses, and can resuscitate when conditions are favorable. Understanding key bacterial proteins can lead to novel therapies.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Hong Wang, Li Wan, Jiahui Shi, Tao Zhang, Huiming Zhu, Songhao Jiang, Shuhong Meng, Shujia Wu, Jinshuai Sun, Lei Chang, Liqun Zhang, Kanglin Wan, Jiaqi Yang, Xiuqin Zhao, Haican Liu, Yao Zhang, Erhei Dai, Ping Xu
Summary: Different strains of Mycobacterium tuberculosis complex (MTBC) exhibit high similarity but show differences in virulence, immune response, and transmissibility. Proteomic analysis of virulent H37Rv, attenuated H37Ra, and avirulent M. bovis BCG vaccine strains revealed minimal expression differences between H37Ra and H37Rv in different growth phases, while significant dysregulation was observed in H37Ra and H37Rv during log phase. Differences were also noted between BCG and H37Rv, as well as BCG and H37Ra during the stationary phase. Protein abundance patterns were similar between H37Ra and BCG, and between H37Rv and H37Ra in different growth phases. Upregulated proteins in H37Rv and H37Ra during log phase were found to be virulence-related, while dysregulated proteins in BCG were identified as M. tuberculosis response proteins under dormancy conditions. This study provides insights into the pathogenesis of H37Rv, attenuation of H37Ra, and immune protection of BCG.
Editorial Material
Critical Care Medicine
Martin I. Voskuil, Larry S. Schlesinger
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2015)
Article
Immunology
Nicholas D. Walter, Gregory M. Dolganov, Benjamin J. Garcia, William Worodria, Alfred Andama, Emmanuel Musisi, Irene Ayakaka, Tran T. Van, Martin I. Voskuil, Bouke C. de Jong, Rebecca M. Davidson, Tasha E. Fingerlin, Katerina Kechris, Claire Palmer, Payam Nahid, Charles L. Daley, Mark Geraci, Laurence Huang, Adithya Cattamanchi, Michael Strong, Gary K. Schoolnik, John Lucian Davis
JOURNAL OF INFECTIOUS DISEASES
(2015)
Article
Immunology
Nicholas D. Walter, Bouke C. de Jong, Benjamin J. Garcia, Gregory M. Dolganov, William Worodria, Patrick Byanyima, Emmanuel Musisi, Laurence Huang, Edward D. Chan, Tran T. Van, Martin Antonio, Abigail Ayorinde, Midori Kato-Maeda, Payam Nahid, Ann M. Leung, Andrew Yen, Tasha E. Fingerlin, Katerina Kechris, Michael Strong, Martin I. Voskuil, J. Lucian Davis, Gary K. Schoolnik
JOURNAL OF INFECTIOUS DISEASES
(2016)
Article
Multidisciplinary Sciences
Anna D. Tischler, Rachel L. Leistikow, Pavithra Ramakrishnan, Martin I. Voskuil, John D. McKinney
Article
Immunology
Benjamin J. Garcia, Andre G. Loxton, Gregory M. Dolganov, Tran T. Van, J. Lucian Davis, Bouke C. de Jong, Martin I. Voskuil, Sonia M. Leach, Gary K. Schoolnik, Gerhard Walzl, Michael Strong, Nicholas D. Walter
Article
Chemistry, Medicinal
Scott M. Irwin, Brendan Prideaux, Edward R. Lyon, Matthew D. Zimmerman, Elizabeth J. Brooks, Christopher A. Schrupp, Chao Chen, Matthew J. Reichlen, Bryce C. Asay, Martin I. Voskuil, Eric L. Nuermberger, Koen Andries, Michael A. Lyons, Veronique Dartois, Anne J. Lenaerts
ACS INFECTIOUS DISEASES
(2016)
Article
Microbiology
I. L. Bartek, M. J. Reichlen, R. W. Honaker, R. L. Leistikow, E. T. Clambey, M. S. Scobey, A. B. Hinds, S. E. Born, C. R. Covey, M. J. Schurr, A. J. Lenaerts, M. I. Voskuil
Article
Microbiology
Matthew J. Reichlen, Rachel L. Leistikow, Micah S. Scobey, Sarah E. M. Born, Martin I. Voskuil
JOURNAL OF BACTERIOLOGY
(2017)
Article
Microbiology
Scott M. Irwin, Veronica Gruppo, Elizabeth Brooks, Janet Gilliland, Michael Scherman, Matthew J. Reichlen, Rachel Leistikow, Igor Kramnik, Eric L. Nuermberger, Martin I. Voskuil, Anne J. Lenaerts
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2014)
Article
Microbiology
I. L. Bartek, L. K. Woolhiser, A. D. Baughn, R. J. Basaraba, W. R. Jacobs, A. J. Lenaerts, M. I. Voskuil
Article
Biochemistry & Molecular Biology
Kawther Alqaseer, Obolbek Turapov, Philippe Barthe, Heena Jagatia, Angelique De Visch, Christian Roumestand, Malgorzata Wegrzyn, Iona L. Bartek, Martin Voskuil, Helen M. O'Hare, Paul Ajuh, Andrew R. Bottrill, Adam A. Witney, Martin Cohen-Gonsaud, Simon J. Waddell, Galina Mukamolova
MOLECULAR MICROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Benjamin T. Grosse-Siestrup, Tuhina Gupta, Shelly Helms, Samantha L. Tucker, Martin I. Voskuil, Frederick D. Quinn, Russell K. Karls
Summary: Sigma factor C (SigC) plays a role in preventing copper starvation in Mycobacterium tuberculosis and regulates the expression of copper-related genes. Deletion of sigC leads to growth defects in a copper-deficient environment and differential expression of 40 genes, including those related to nonribosomal peptide synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Nicholas D. Walter, Sarah E. M. Born, Gregory T. Robertson, Matthew Reichlen, Christian Dide-Agossou, Victoria A. Ektnitphong, Karen Rossmassler, Michelle E. Ramey, Allison A. Bauman, Victor Ozols, Shelby C. Bearrows, Gary Schoolnik, Gregory Dolganov, Benjamin Garcia, Emmanuel Musisi, William Worodria, Laurence Huang, J. Lucian Davis, Nhung V. Nguyen, Hung V. Nguyen, Anh T. V. Nguyen, Ha Phan, Carol Wilusz, Brendan K. Podell, N' Dira Sanoussi, Bouke C. de Jong, Corinne S. Merle, Dissou Affolabi, Helen McIlleron, Maria Garcia-Cremades, Ekaterina Maidji, Franceen Eshun-Wilson, Brandon Aguilar-Rodriguez, Dhuvarakesh Karthikeyan, Khisimuzi Mdluli, Cathy Bansbach, Anne J. Lenaerts, Radojka M. Savic, Payam Nahid, Joshua J. Vasquez, Martin I. Voskuil
Summary: The study demonstrates that sterilizing drugs and highly effective drug regimens profoundly suppress Mycobacterium tuberculosis rRNA synthesis, while non-sterilizing drugs and weaker regimens do not. Utilizing the rRNA synthesis ratio as a metric of drug activity may accelerate the development of shorter tuberculosis treatment regimens.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Emmanuel Musisi, Christian Dide-Agossou, Reem Al Mubarak, Karen Rossmassler, Abdul Wahab Ssesolo, Sylvia Kaswabuli, Patrick Byanyima, Ingvar Sanyu, Josephine Zawedde, William Worodria, Martin Voskuil, Rada M. Savic, Payam Nahid, J. Lucian Davis, Laurence Huang, Camille M. Moore, Nicholas D. Walter
Summary: The RS ratio, a novel pharmacodynamic marker, shows high repeatability and reproducibility in sputum samples from Ugandan adults with drug-susceptible pulmonary TB. It measures a distinct property independent of M. tuberculosis burden, providing valuable information beyond traditional markers of bacterial burden.
MICROBIOLOGY SPECTRUM
(2021)
Article
Microbiology
Christian Dide-Agossou, Allison A. Bauman, Michelle E. Ramey, Karen Rossmassler, Reem Al Mubarak, Samantha Pauly, Martin Voskuil, Maria Garcia-Cremades, Rada M. Savic, Payam Nahid, Camille M. Moore, Rokeya Tasneen, Eric L. Nuermberger, Gregory T. Robertson, Nicholas D. Walter
Summary: This study evaluated the ability of different pharmacodynamic markers to distinguish between treatments in murine tuberculosis drug efficacy studies. The combination of pharmacodynamic markers, especially the RS ratio and CFU, showed the greatest ability to recapitulate the rank order of regimen treatment-shortening activity, accelerating the development of new combination regimens.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)