Article
Biochemistry & Molecular Biology
Saloni Rajesh Wani, Vikas Jain
Summary: The study reveals that M. smegmatis MscR exhibits mycothiol-independent formaldehyde dehydrogenase activity in vitro, with zinc enhancing its activity. Additionally, MscR only uses formaldehyde as its substrate and M. smegmatis lacking MscR shows increased sensitivity to formaldehyde. Investigation of conserved cysteines in MscRs from various bacteria demonstrates their importance in structural stability and enzymatic activity.
Article
Biology
Pradeep Kumar Anand, Arbind Kumar, Amrit Saini, Jagdeep Kaur
Summary: In this study, the effect of a mutation in the EthA protein on its function was examined through structural and functional analysis. The results showed that the mutation led to a less stable protein structure and reduced binding affinity towards the anti-tuberculosis drug ETH. In vitro experiments validated the computational findings. The mutant strain exhibited higher growth and survival in the presence of the ETH drug, indicating decreased sensitivity of Mycobacterium tuberculosis to ETH.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2022)
Article
Infectious Diseases
Bin Cao, Xiaokaiti Mijiti, Le-Le Deng, Quan Wang, Jin-Jie Yu, Aiketaguli Anwaierjiang, Chengyu Qian, Machao Li, Dan-Ang Fang, Yi Jiang, Li-Li Zhao, Xiuqin Zhao, Kanglin Wan, Haican Liu, Guilian Li, Xiuqin Yuan
Summary: This study investigated the resistance profiles and genetic mutations conferring resistance to isoniazid (INH) and ethionamide (ETH) in Mycobacterium tuberculosis isolates from the south of Xinjiang, China. The results showed that 28.9% of the isolates were resistant to INH, 10.9% were resistant to ETH, and 8.0% were co-resistant to both. These findings contribute to the understanding of drug resistance mechanisms and can guide clinical treatment and molecular drug susceptibility testing methods.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Immunology
Heather A. Parker, Nina Dickerhof, Lorna Forrester, Heath Ryburn, Leon Smyth, Joris Messens, Htin L. Aung, Gregory M Cook, Anthony J. Kettle, Mark B. Hampton
Summary: The study found that M. smegmatis can resist the HOCl produced inside neutrophil phagosomes, and the main reason may not be its main low-molecular-weight thiol. These findings provide new opportunities for research on how to enhance the destruction of pathogenic mycobacteria by the immune system.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Muluwork Getahun, Henry M. Blumberg, Gobena Ameni, Dereje Beyene, Russell R. Kempker
Summary: This study evaluated the minimum inhibitory concentrations (MICs) of multidrug resistant (MDR) and rifampin resistant (RR) as well as isoniazid (INH) resistant Mtb isolates to determine the level of drug resistance for key anti-tuberculosis drugs. It was found that a subset of INH resistant isolates had borderline rifampin resistance and a high proportion of MDR TB isolates had moderate level isoniazid resistance, indicating the potential benefit of high dose isoniazid treatment.
Article
Biotechnology & Applied Microbiology
Jijimole Gopi Reji, Lakshmi K. Edison, Sajith Raghunandanan, Akhil Raj Pushparajan, Krishna Kurthkoti, Ramakrsihnan Ajay Kumar
Summary: The expression of Rv1255c gene is upregulated during dormancy and it helps M. tuberculosis tolerate isoniazid by orchestrating drug efflux machinery. In addition, Rv1255c also causes overexpression of katG isoform in M. tuberculosis which has amino acid substitutions associated with isoniazid resistance.
JOURNAL OF ANTIBIOTICS
(2023)
Article
Medicine, General & Internal
Alexander D. Giddey, Tariq A. Ganief, Naadir Ganief, Anastasia Koch, Digby F. Warner, Nelson C. Soares, Jonathan M. Blackburn
Summary: The study investigated the proteomic response of rifampicin-resistant M. smegmatis strain, revealing some similar responses to the wild type strain and supporting the hypothesis of Rifampicin's RpoB-independent effects at sublethal doses.
FRONTIERS IN MEDICINE
(2021)
Review
Microbiology
Afsatou Ndama Traore, Mpumelelo Casper Rikhotso, Marry Avheani Mphaphuli, Sana Mustakahmed Patel, Hafsa Ali Mahamud, Leonard Owino Kachienga, Jean-Pierre Kabue, Natasha Potgieter
Summary: This review and meta-analysis investigated the prevalence and molecular insights into isoniazid (INH) and rifampicin (RIF) resistance-conferring mutations in Mycobacterium tuberculosis isolates from South Africa. High prevalence of specific mutations, including S450L in rpoB and S315T, linked to resistance against RIF and INH respectively, were found. These findings contribute to understanding drug resistance mechanisms and provide valuable insights for targeted interventions against drug-resistant TB.
Article
Multidisciplinary Sciences
Aditya Kumar Pal, Anirban Ghosh
Summary: This study investigates the role of secondary messenger c-di-AMP in drug tolerance, specifically in Mycobacterium smegmatis. The findings highlight the specific molecular mechanism linking elevated c-di-AMP levels with resistance mutagenesis and emphasize the significance of non-homology-based DNA repair. Additionally, the study identifies the unique mutational landscape associated with intracellular c-di-AMP levels and demonstrates the critical role of c-di-AMP in driving the evolution of multi-drug tolerance.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Anwar Sheed Khan, Jody E. Phelan, Muhammad Tahir Khan, Sajid Ali, Muhammad Qasim, Noor Mohammad, Gary Napier, Sajjad Ahmad, Jamshed Alam, Baharullah Khattak, Susana Campino, Taane G. Clark, Taj Ali Khan
Summary: Tuberculosis is a major public health issue in Pakistan, and the study on genetic mutations of candidate genes contributes to the management and control of drug-resistant TB in the region. The most common resistance mutations were found in katG, fabG1, and inhA genes, with other rare mutations also identified.
Article
Infectious Diseases
Arata Sakiyama, Ken-Ichi Oinuma, Yukihiro Kaneko
Summary: This study aims to reveal the mechanism underlying the INH-dependent induction of PzaA. Through transcriptomic analysis, a gene cluster containing MSMEI_1050 was identified to play a key role in INH-dependent gene regulation.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2023)
Article
Immunology
Saba Naz, Yogendra Singh, Vinay Kumar Nandicoori
Summary: The study reveals that the serine/threonine-protein kinase PknL in Mycobacterium tuberculosis plays a crucial role in regulating stress response and infection establishment in the host. Deletion of pknL results in compromised bacterial growth under redox stress, reduced ability to establish infections in peritoneal macrophages and disseminate to the spleen in a murine infection model. Additionally, the absence of pknL enhances survival upon isoniazid or ethambutol treatment, suggesting a potential role in reducing the efficacy of these antibiotics.
Article
Microbiology
Shadi Parsa, Atieh Yaghoubi, Nafiseh Izadi, Faezeh Sabet, Leila babaei Nik, Mohammad Derakhshan, Seyed Abdolrahim Rezaee, Zahra Meshkat, Seyed Javad Hoseini, Saeid Amel Jmehdar, Fatemeh Kiani, Amin Samiei, Saman Soleimanpour
Summary: This study compared the diagnostic accuracy of high-resolution melting-curve analysis (HRMA) with other commonly used methods for detecting INH and RIF resistance in drug-resistant tuberculosis. The results showed that using HRMA with the target of the katG gene and the mabA-inhA promoter region can improve the sensitivity and specificity.
CURRENT MICROBIOLOGY
(2022)
Article
Medicine, Research & Experimental
Jingying Guo, Xiaobo Ma, Jennifer M. Skidmore, Jelka Cimerman, Diane M. Prieskorn, Lisa A. Beyer, Donald L. Swiderski, David F. Dolan, Donna M. Martin, Yehoash Raphael
Summary: Pathogenic variants in GJB2 are the most common cause of autosomal-recessive hereditary deafness, but the mechanisms leading to GJB2-related deafness are not well understood and effective treatments are lacking. Mouse models show that conditional loss of Gjb2 results in extensive loss of cochlear hair cells and neurons, hindering therapies that require intact cochlear cells. Attempts to rescue the phenotype in a less severe model showed some promising results within a 2-month timeframe.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Medical Laboratory Technology
E. Benaissa, Y. Benlahlou, F. Bssaibis, A. Maleb, M. Elouennass
Summary: This study evaluated the performance of the GenoType MTBDRplus assay in detecting rifampicin and isoniazid resistance in Mycobacterium tuberculosis isolates in a Moroccan hospital, and determined the frequency of mutations associated with resistance to these two drugs. The results showed that the GenoType MTBDRplus assay has high sensitivity and specificity for the detection of rifampicin and isoniazid resistance.
CLINICAL LABORATORY
(2022)
Review
Immunology
Aaron J. Moulson, Yossef Av-Gay
Summary: The century-old BCG vaccine has gained renewed interest for its ability to protect against various non-TB pathogens, with potential for use as an immunotherapeutic agent for autoimmune, allergic, neurodegenerative, and neoplastic diseases as well as a preventive measure against infections. Particularly noteworthy is its proposed use in countering the rise of autoimmune and allergic conditions, as well as its potential in mitigating the spread of COVID-19 until a specific vaccine is developed.
Article
Microbiology
Catherine Vilcheze, Steven A. Porcelli, John Chan, William R. Jacobs
Summary: Study found that specific strains of Mycobacterium tuberculosis can alter their bactericidal properties through leucine and pantothenate auxotrophy, rather than arginine auxotrophy. These triple-auxotrophic strains are crucial for understanding the bacterial and host factors leading to persistent infection of M. tuberculosis as well as for vaccine development studies.
Article
Microbiology
Catherine Vilcheze, William R. Jacobs
Summary: NAC shows boosting activity with TB drugs in vitro, but does not enhance the activity of TB drugs in infected mice models, suggesting differences between in vitro and in vivo effects.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Microbiology
Celine Rens, Joseph D. Chao, Danielle L. Sexton, Elitza Tocheva, Yossef Av-Gay
Summary: PDIMs are complex lipids found in the cell envelope of Mycobacterium tuberculosis that play a key role in the pathogenesis of the bacterium, particularly in bacterial virulence and in association with the ESX-1 secretion system. However, the mechanisms by which PDIMs help M. tuberculosis to control macrophage phagocytosis, inhibit phagosome acidification and modulate host innate immunity are still not fully understood.
Review
Microbiology
Leah Isobella Rankine-Wilson, Tirosh Shapira, Carine Sao Emani, Yossef Av-Gay
Summary: Tuberculosis, caused by Mycobacterium tuberculosis, is a serious disease that requires lengthy and complicated treatment. Understanding the physiological mechanisms of Mtb can lead to the development of more effective drug therapies.
Editorial Material
Microbiology
Yossef Av-Gay, Giorgia Mori, Maria Rosalia Pasca
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemical Research Methods
Celine Rens, Tirosh Shapira, Sandra Pena-Diaz, Joseph D. Chao, Tom Pfeifer, Yossef Av-Gay
Summary: The authors developed AUTOptosis, a cost-effective and rapid apoptosis monitoring method based on quantifying nuclei intensity via staining with Hoechst 33342. They calibrated the method with standard apoptosis inducers in multiple cell lines, validated its applicability for high-content screening using a compound library, and demonstrated its specificity by detecting apoptosis triggered by Mycobacterium tuberculosis infections. AUTOptosis method involves morphological analysis of nuclear condensation during caspase-3-dependent apoptosis, where Hoechst-stained nuclei appear brighter during apoptosis and fade during necrosis, providing an apoptosis index for comparing test and control conditions.
Article
Chemistry, Medicinal
Adrian Richter, Gagandeep Narula, Ines Rudolph, Ruediger W. Seidel, Christoph Wagner, Yossef Av-Gay, Peter Imming
Summary: 8-Nitrobenzothiazinones (BTZs) are a promising class of antimycobacterial agents currently being investigated in clinical trials. A new synthetic pathway has been established to synthesize various analogues of BTZs, allowing the replacement of the sulphur atom by oxygen or nitrogen. A total of 36 analogues were synthesized and tested for their potential activity against Mycobacterium tuberculosis (Mtb) in in vitro assays.
Article
Biotechnology & Applied Microbiology
Henok A. Sahile, David E. Williams, Nicole J. de Voogd, Mary Ko, Raymond J. Andersen, Yossef Av-Gay
Summary: Screening and isolation of marine derived crude natural products led to the discovery of 10 hits with activity against Mycobacterium tuberculosis (Mtb). Among them, lissoclinotoxin F (1) showed the highest potency and selectivity, and could be a potential lead compound for the development of new TB drugs.
JOURNAL OF ANTIBIOTICS
(2022)
Article
Biochemistry & Molecular Biology
Clement K. M. Tsui, Flavia Sorrentino, Gagandeep Narula, Alfonso Mendoza-Losana, Ruben Gonzalez del Rio, Esther Perez Herran, Abraham Lopez, Adama Bojang, Xingji Zheng, Modesto Jesus Remuinan-Blanco, Yossef Av-Gay
Summary: Through chemical-genetic characterization and whole genome sequencing analysis, novel drug targets and drug resistance genes associated with Mycobacterium tuberculosis (Mtb) intracellular growth were identified. The exploration of Mtb chemical mutant genomes could aid in novel drug discovery and the understanding of tuberculosis treatment mechanisms.
Article
Microbiology
Rajagopalan Saranathan, Emmanuel Asare, Lawrence Leung, Anna Paula de Oliveira, Katherine E. Kaugars, Claire Mulholland, Regy Lukose, Michael Berney, William R. Jacobs
Summary: Optimizing Oxford Nanopore Technology (ONT) allows us to capture the entire genome of herpes simplex virus (HSV) as a single read, and we have reported for the first time the full-length genomes of all four variants. This will contribute to the understanding of the significance and clinical relevance of these variants in HSV-1 infections.
MICROBIOLOGY SPECTRUM
(2022)
Review
Microbiology
Ian L. Sparks, Keith M. Derbyshire, William R. Jacobs Jr, Yasu S. Morita
Summary: Mycobacterium smegmatis is a nonpathogenic and fast growing species that has been elevated to model status for mycobacterial research, providing valuable insights into other pathogens within this genus.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Multidisciplinary Sciences
Miguel Dario Prieto, Jiah Jang, Alessandro N. Franciosi, Yossef Av-Gay, Horacio Bach, Scott J. Tebbutt, Bradley S. Quon
Summary: This study found that patients with cystic fibrosis who develop non-tuberculous mycobacteria pulmonary disease (NTM-PD) exhibit enhanced innate immune responses, which is different from the non-cystic fibrosis population.
Article
Biochemistry & Molecular Biology
Tirosh Shapira, Selvarani Vimalanathan, Celine Rens, Virginia Pichler, Sandra Pena-Diaz, Grace Jordana, William Rees, Dirk F. H. Winkler, Iqbal Sarai, Theodore Steiner, Francois Jean, Steven Pelech, Yossef Av-Gay
Summary: GSK3 beta inhibitors have shown broad-spectrum anti-coronaviridae activity, including against SARS-CoV-2, with low toxicity to host cells. A lead compound, T-1686568, exhibited dose-dependent activity against SARS-CoV-2 and HCoV-229E and showed efficacy in viral-infected cells and organoids. GSK3 beta and PKCa can phosphorylate the nucleocapsid protein of SARS-CoV-2, inhibiting its translation.
MOLECULAR BIOMEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Rosanne Persaud, Sheena C. Li, Joseph D. Chao, Roberto Forestieri, Elizabeth Donohue, Aruna D. Balgi, Xingji Zheng, Jesse T. Chao, Yoko Yashiroda, Mami Yoshimura, Christopher J. R. Loewen, Anne-Claude Gingras, Charles Boone, Yossef Av-Gay, Michel Roberge, Raymond J. Andersen
Summary: A study found that the marine natural product clionamines can activate autophagy and inhibit the survival of Mycobacterium tuberculosis in macrophages. Pik1 was identified as the target protein of clionamines using a yeast chemical-genetics approach. Further research revealed that PI4KB is an unexploited molecular target that, when knocked down, can inhibit the survival of Mycobacterium tuberculosis in macrophages.
CELL CHEMICAL BIOLOGY
(2022)