Article
Microbiology
Gopinath Krishnamoorthy, Peggy Kaiser, Patricia Constant, Ulrike Abu Abed, Monika Schmid, Christian K. Frese, Volker Brinkmann, Mamadou Daffe, Stefan H. E. Kaufmann
Summary: Mycofactocin, a peptide-derived redox cofactor, is found in certain bacteria like Mycobacterium tuberculosis. Research indicates that mftD gene expression is upregulated in hypoxia-adapted M. tuberculosis, but its functionality may not be essential for L-lactate metabolism. The study highlights the potential significance of mycofactocin in bacterial growth and persistence within the host.
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
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)
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
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
Microbiology
Yongjie Zhao, Shengwen Shang, Ya Song, Tianyue Li, Mingliang Han, Yuexuan Qin, Meili Wei, Jun Xi, Bikui Tang
Summary: Sulforaphane (SFN) exhibits antimycobacterial activity against Mycobacterium tuberculosis by increasing bacterial reactive oxygen species (ROS) levels and promoting the bactericidal effect of macrophages. This discovery provides important insights for the development of new host-directed therapeutic approaches against tuberculosis.
JOURNAL OF MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mehak Zahoor Khan, Biplab Singha, Mohammad Farhan Ali, Khushman Taunk, Srikanth Rapole, Samudrala Gourinath, Vinay Kumar Nandicoori
Summary: The study identified AosR as a crucial transcription factor for Mycobacterium tuberculosis survival in the host by mitigating oxidative and nitrosative stress, and promoting growth in the murine lungs and spleen. AosR interacts with SigH to upregulate CysM-dependent cysteine biosynthesis pathway, which is essential for detoxifying host-derived radicals and enhancing bacterial survival in the intracellular environment.
Article
Immunology
Jessica Comin, Jan Madacki, Isabel Rabanaque, Maria Zuniga-Anton, Daniel Ibarz, Alberto Cebollada, Jesus Vinuelas, Luis Torres, Juan Sahagun, Christophe Klopp, Jesus Gonzalo-Asensio, Roland Brosch, Maria-Jose Iglesias, Sofia Samper
Summary: Through analysis of a tuberculosis outbreak and molecular characteristics of the MtZ strain, several SNPs in genes related to virulence, pathogenesis, and survival, as well as other genomic polymorphisms, were identified, which may contribute to its success in transmission among the population.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Immunology
Haotian Bo, Ulrich Aymard Ekomi Moure, Yuanmiao Yang, Jun Pan, Li Li, Miao Wang, Xiaoxue Ke, Hongjuan Cui
Summary: Mycobacterium tuberculosis (Mtb), the causative agent of TB, interacts with macrophages in the lungs, subverting the host immune system and causing infection. This review examines Mtb effectors that interact with macrophages and how macrophages control and eliminate Mtb, as well as how Mtb manipulates macrophage defense mechanisms for its own survival. Understanding these mechanisms is crucial for TB prevention, diagnosis, and treatment.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Microbiology
Robeena Farzand, Richard D. Haigh, Philip Monk, Pranabashis Haldar, Hemu Patel, Manish Pareek, Raman Verma, Michael R. Barer, Gerrit Woltmann, Lauren Ahyow, Heena Jagatia, Jonathan Decker, Galina V. Mukamolova, Andrea M. Cooper, Natalie J. Garton, Helen M. O'Hare
Summary: The genetic diversity of Mycobacterium tuberculosis plays a role in disease severity and transmissibility. In this study, the phenotyping of M. tuberculosis from a persistent outbreak in the UK revealed higher lipid contents and more hydrophobic cell surfaces compared to nonoutbreak isolates. Deletions in specific genes were also found in the outbreak isolates, potentially altering the interactions between the bacteria and immune cells. Reintroduction of one of these genes led to a phenotype resembling nonoutbreak strains. Understanding the microbiological characteristics and genetic polymorphisms associated with outbreaks can inform tuberculosis control strategies.
Article
Biochemistry & Molecular Biology
Mubarak A. Alamri, Sajjad Ahmad, Safar M. Alqahtani, Muhammad Irfan, Alhumaidi B. Alabbas, Muhammad Tahir Ul Qamar
Summary: Tuberculosis remains a major global public health concern. The development of new drugs is necessary due to the emergence of drug-resistant strains of Mycobacterium tuberculosis. In this study, comprehensive computational methods were used to identify compounds that bind to essential enzymes involved in biotin synthesis and ligation of M. tuberculosis. Two compounds were found to consistently bind to the enzymes with high affinity. These compounds could potentially be used in the design of effective anti-tuberculosis therapeutics by inhibiting bacterial growth through blocking biotin biosynthesis.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
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
Biology
Fabrizio Menardo, Caroline Colijn
Summary: Detecting factors associated with transmission is crucial for understanding disease epidemics and designing effective public health measures. In this study, the author used a simulation-based approach to investigate the influence of various epidemiological processes on clustering and TBL analyses of Mycobacterium tuberculosis genomic data sets. The results show that different factors, except the length of the infectious period, affect the outcomes of clustering and TBL distributions. The study also highlights the limitations of current interpretations of these analyses and suggests that optimal clustering thresholds and TBL distributions may vary depending on epidemiological conditions.
Article
Microbiology
Ruoyao Ma, Damien Farrell, Gabriel Gonzalez, John A. Browne, Chie Nakajima, Yasuhiko Suzuki, Stephen Gordon
Summary: This study investigates the function of the TbD1 locus in Mycobacterium bovis and its role in stress responses, revealing its impact on the sensitivity to oxidative stress and hypoxia-specific copper toxicity in M. bovis strains.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Michael Ramek, Jasmina Sabolovic
Summary: This paper investigates the geometries, energy landscapes, and magnetic parameters of copper(II) amino acid compounds using density functional theory calculations. The results show that certain conformers with histaminate-like and glycine-like modes have low Gibbs free energies and high metal-binding affinities. The predicted conformations reproduce the experimental electron paramagnetic resonance parameters.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Wei Tian, Wen Zhong, Zengyan Yang, Ling Chen, Shijie Lin, Yanping Li, Yuxing Wang, Peilin Yang, Xing Long
Summary: A series of novel dibutyltin complexes based on salen-like ligands were synthesized and characterized. Complex S03 showed excellent in vitro anticancer activity and induced cancer cell death through multiple mechanisms. This study reveals new mechanisms of organotin complexes and provides new insights into the development of organotin metal complexes as anticancer drugs.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Natalie C. Korkola, Martin J. Stillman
Summary: Many proteins require a metal cofactor for their function, and these metals play a role in protein folding. The study found that the metallation rates of different metal binding pathways are influenced by pH, with the less cooperative pathway being more affected by low pH conditions. Specific mixtures of structures are formed in the initial steps of metallation, and unfolding the disordered apo-MT structure hinders the formation of these preliminary structures. The compact conformation of the native apo-MT allows for rapid formation of metal-thiolate structures with high affinity, providing protection from oxidation.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Boxuan Yang, Xitong Song, Binju Wang
Summary: The diiron active site plays a crucial role in catalytic transformations in both biological and chemical systems. Recent advancements in the field include the synthesis of biomimetic diiron catalysts inspired by the active structure of soluble methane monooxygenase (sMMO), which have been successfully applied to the dehydrogenation of indolines.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Christina N. Banti, Angeliki A. Piperoudi, Catherine P. Raptopoulou, Vassilis Psycharis, Constantinos M. Athanassopoulos, Sotiris K. Hadjikakou
Summary: Two copper(I) polymorphs with mitochondria-targeting properties were successfully prepared via metal ion conjugation. These compounds showed promising activities in DNA binding, enzyme inhibition, and cancer cell inhibition. The molecular mechanisms of action were investigated.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)