Article
Medicine, Research & Experimental
Riti Sharan, Shashank R. Ganatra, Dhiraj K. Singh, Journey Cole, Taylor W. Foreman, Rajesh Thippeshappa, Charles A. Peloquin, Vinay Shivanna, Olga Gonzalez, Cheryl L. Day, Neel R. Gandhi, Edward J. Dick Jr, Shannan Hall-Ursone, Smriti Mehra, Larry S. Schlesinger, Jyothi Rengarajan, Deepak Kaushal
Summary: The study found that 3HP treatment significantly reduced the infection of Mycobacterium tuberculosis and prevented reactivation of tuberculosis in latently infected macaques.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Medicine, Research & Experimental
Riti Sharan, Shashank R. Ganatra, Dhiraj K. Singh, Journey Cole, Taylor W. Foreman, Rajesh Thippeshappa, Charles A. Peloquin, Vinay Shivanna, Olga Gonzalez, Cheryl L. Day, Neel R. Gandhi, Edward J. Dick, Shannan Hall-Ursone, Smriti Mehra, Larry S. Schlesinger, Jyothi Rengarajan, Deepak Kaushal
Summary: This study assessed the clearance of M. tuberculosis bacteria in macaques with asymptomatic LTBI following a three-month treatment of 3HP. The results showed that most of the treated macaques did not have persistent bacterial infection or extrapulmonary spread, while the untreated macaques harbored persistent bacterial infection and experienced tuberculosis reactivation following SIV coinfection. This suggests that 3HP treatment effectively reduces tuberculosis infection and prevents reactivation of latent tuberculosis in macaques.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Infectious Diseases
Manita Yimcharoen, Sukanya Saikaew, Usanee Wattananandkul, Ponrut Phunpae, Sorasak Intorasoot, Chatchai Tayapiwatana, Bordin Butr-Indr
Summary: This study investigated the adaptive responses of Mycobacterium tuberculosis to isoniazid treatment using a multi-stress system. The expression of stressresponse and lipoarabinomannan-related genes were measured, revealing different adaptations between drug-resistant and drug-susceptible strains. The study demonstrates the complexity of mycobacterial adaptation and provides potential applications for tuberculosis treatment and monitoring in the future.
Article
Pharmacology & Pharmacy
Peipei Qiao, Yingbing Zhang, Ying Yang, Ru Meng, Zhiming Xu, Xianlei Jiang, Yong Zhang, Chengtu Zhang, Jianmin Su
Summary: Isoniazid (INH) significantly impairs meiotic progression, increases oxidative stress, induces apoptosis, and disrupts mitochondrial function in mouse oocytes. These effects ultimately lead to reduced fertility and damage to the mammalian reproductive system.
Review
Biochemistry & Molecular Biology
Inesa Navasardyan, Stephanie Yeganyan, Helena Nguyen, Payal Vaghashia, Selvakumar Subbian, Vishwanath Venketaraman
Summary: Tuberculosis meningitis (TBM) occurs when Mycobacterium tuberculosis bacteria invade the meninges, leading to inflammation. Oxidative stress, caused by reactive oxygen species, plays a significant role in TBM by impairing the body's defense mechanisms. Diabetes mellitus (DM) increases susceptibility to TBM due to heightened oxidative stress. This review summarizes the role of oxidative stress in TBM and DM, and discusses potential therapeutic approaches.
Article
Microbiology
K. B. Arun, Aravind Madhavan, Billu Abraham, M. Balaji, K. C. Sivakumar, P. Nisha, R. Ajay Kumar
Summary: Isoniazid (INH) is activated by the KatG enzyme of Mycobacterium tuberculosis and inhibits cell wall biosynthesis. INH-resistant strains often have mutations in specific genes, but some strains may use alternative mechanisms. A study found that Rv2170 acetylates INH, potentially contributing to drug resistance.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Gunapati Bhargavi, Amit Kumar Singh, Anbarasu Deenadayalan, Chinnaiyan Ponnuraja, Shripad A. Patil, Kannan Palaniyandi
Summary: This study investigates the stress response and virulence of M. tuberculosis, and reports the functional characterization of an alkylhydroperoxidase family member, Rv2159c. The study reveals that Rv2159c plays a significant role in maintaining cellular homeostasis, reducing oxidative stress, and countering toxic metals.
Article
Biochemistry & Molecular Biology
Damiano Rocchi, Juan F. Gonzalez, Olmo Martin-Camara, Maria Grazia Perrone, Morena Miciaccia, Antonio Scilimati, Celine Decouty-Perez, Esther Parada, Javier Egea, J. Carlos Menendez
Summary: This study found that m-terphenylamine derivatives are selective inhibitors of cyclooxygenase-1 (COX-1), able to block microglia inflammatory response and elicit a neuroprotective effect.
Article
Infectious Diseases
Manita Yimcharoen, Sukanya Saikaew, Usanee Wattananandkul, Ponrut Phunpae, Sorasak Intorasoot, Watchara Kasinrerk, Chatchai Tayapiwatana, Bordin Butr-Indr
Summary: This study explores the impact of isoniazid stress on the regulation of ManLAM-related genes in Mycobacterium tuberculosis with different drug resistance profiles. The results show distinct gene expression patterns between drug-resistant and drug-sensitive TB samples, with a notable upregulation of ManLAM-related genes in drug-resistant strains, particularly multidrug-resistant strains. This novel gene expression pattern provides valuable insights for future tuberculosis monitoring and treatment.
INFECTION AND DRUG RESISTANCE
(2022)
Article
Medicine, General & Internal
Christopher Pease, Gonzalo Alvarez, Ranjeeta Mallick, Mike Patterson, Sandy Finn, Yahya Habis, Kevin Schwartzman, Elaine Kilabuk, Sunita Mulpuru, Alice Zwerling
Summary: The study suggests that using once weekly rifapentine and isoniazid for 12 weeks (3HP) for LTBI treatment in the remote Canadian Arctic community of Iqaluit may lead to cost savings and similar or improved health outcomes compared to the current standard care.
Article
Immunology
Courtney M. Yuen, Arman Majidulla, Maria Jaswal, Nauman Safdar, Amyn A. Malik, Aamir J. Khan, Mercedes C. Becerra, Salmaan Keshavjee, Chunling Lu, Hamidah Hussain
Summary: The study compared the economic costs of delivering two tuberculosis preventive treatment regimens in Karachi, Pakistan, finding that the cost per completed course was lower for the 3HP regimen compared to the 6H regimen, driven by higher completion rates in the high-tuberculosis-burden setting.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Immunology
Adriana Weinberg, Lisa Aaron, Grace Montepiedra, Timothy R. Sterling, Renee Browning, Blandina Mmbaga, Tichaona Vhembo, Shilpa Naik, Enid Kabugho, Gaerolwe Masheto, Savita Pahwa, Jyoti S. Mathad, Sylvia M. LaCourse, Katie McCarthy, Sarah Bradford, Gerhard Theron, Diane Costello, Bonnie Zimmer, Marie F. Pierre, Kamunkhwala Gausi, Paolo Denti, David W. Haas, Amita Gupta
Summary: This study found that immune suppression during pregnancy may lead to decreased QuantiFERON-gold-in-tube (QGIT) positivity for latent tuberculosis infection (LTBI) due to reduced interferon gamma responses. Tuberculin skin test (TST) was less affected by pregnancy and had lower positivity compared to QGIT. Isoniazid preventive therapy (IPT) was associated with loss of QGIT positivity, suggesting potential clinical implications that need further investigation.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Chemistry, Multidisciplinary
Ruoqiong Cao, Afsal Kolloli, Ranjeet Kumar, James Owens, Kayvan Sasaninia, Charles Vaughn, Mohkam Singh, Edward Truong, Nala Kachour, Abrianna Beever, Wael Khamas, Selvakumar Subbian, Vishwanath Venketaraman
Summary: In an in vivo mouse model of active M. tb infection, diethyl maleate (DEM)-induced glutathione (GSH) deficiency led to increased oxidative stress, impaired granuloma response, and increased M. tb survival. These findings provide insights into how GSH deficiency can interfere with the control of M. tb infection.
APPLIED SCIENCES-BASEL
(2021)
Article
Biochemistry & Molecular Biology
Andrea Sanchez-Navarro, Adrian Rafael Murillo-de-Ozores, Rosalba Perez-Villalva, Nadyeli Linares, Hector Carbajal-Contreras, Maria Elena Flores, Gerardo Gamba, Maria Castaneda-Bueno, Norma A. Bobadilla
Summary: This study demonstrates the relocation of serpinA3c/k to the apical tubular membrane in chronic kidney disease and its increased secretion during cellular stress. Atypical urinary excretion of serpinA3c/k was also observed in acute kidney injury, suggesting its potential as a biomarker for AKI.
Article
Microbiology
Stefanie Krug, Pankaj Prasad, Shiqi Xiao, Shichun Lun, Camilo A. A. Ruiz-Bedoya, Mariah Klunk, Alvaro A. A. Ordonez, Sanjay K. K. Jain, Geetha Srikrishna, Igor Kramnik, William R. R. Bishai
Summary: Despite advances in TB drug development, multidrug resistance remains a major challenge for global TB control. Host-directed therapies, such as inhibition of the integrated stress response (ISR), have the potential to improve the efficacy of tuberculosis antibiotics. In this study, we evaluated the impact of ISR inhibition on bacterial clearance, relapse, and lung pathology in a mouse model of TB. Our findings suggest that adjunctive ISR inhibition can accelerate bacterial clearance, reduce relapse rates, and improve lung health.
Article
Multidisciplinary Sciences
Kurinchi S. Gurusamy, David Moher, Marilena Loizidou, Irfan Ahmed, Marc T. Avey, Carly C. Barron, Brian Davidson, Miriam Dwek, Christian Gluud, Gavin Jell, Kiran Katakam, Joshua Montroy, Timothy D. McHugh, Nicola J. Osborne, Merel Ritskes-Hoitinga, Kees van Laarhoven, Jan Vollert, Manoj Lalu
Summary: The study developed a tool to assess the clinical relevance of preclinical studies and refined and developed it using a modified Delphi consensus. The tool consists of eight domains and 28 signaling questions, providing a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research.
Article
Veterinary Sciences
J. D. Fonseca, D. E. Mavrides, P. A. Graham, T. D. McHugh
Summary: Bacterial urinary tract infections are common in small animals, with Escherichia coli being the most prevalent species. Resistance to commonly used antibiotics such as ampicillin and amoxicillin-clavulanic acid is emerging, highlighting the need for continued monitoring of antibiotic resistance in uropathogens. Despite this, fluoroquinolones continue to show good in vitro activity against uropathogens.
JOURNAL OF SMALL ANIMAL PRACTICE
(2021)
Article
Veterinary Sciences
Daphne E. Mavrides, Alice L. Morgan, Jea G. Na, Peter A. Graham, Timothy D. McHugh
Summary: Bacterial lower respiratory tract infections (bLRTIs) are common and potentially life threatening in cats and dogs. Antibiotic treatment is often initiated before the diagnosis of bLRTI; therefore improved knowledge of the aetiology and antibiotic susceptibility patterns of these infections is essential to inform empiric antibiotic choices. The study found resistance to certain first-choice antibiotics in bLRTIs, highlighting the need for continued monitoring and sound evidence to inform decision-making in the management of these infections.
Review
Public, Environmental & Occupational Health
Ana Paleckyte, Oshani Dissanayake, Stella Mpagama, Marc C. Lipman, Timothy D. McHugh
Summary: Globally, tuberculosis is a major cause of death and healthcare workers are at increased risk of hospital-acquired TB infection. The World Health Organization has developed an international system of infection prevention and control interventions, but implementation in resource-constrained settings and high TB burden areas is often inadequate. Healthcare workers often underestimate the risk of TB transmission and lack of expertise and funding can lead to unsafe practices and increase the risk of TB dissemination.
ANTIMICROBIAL RESISTANCE AND INFECTION CONTROL
(2021)
Article
Microbiology
Darrel Ornelle Elion Assiana, Jabar Babatunde Pacome Achimi Abdul, Laure Stella Ghoma Linguissi, Micheska Epola, Jeannhey Christevy Vouvoungui, Albert Mabiala, Christopher Mebiame Biyogho, Jean Ronald Edoa, Bayode Romeo Adegbite, Ayola Akim Adegnika, Linzy Elton, Julio Ortiz Canseco, Timothy D. McHugh, Gabriel Ahombo, Francine Ntoumi
Summary: This study in the Republic of Congo implemented molecular tools to diagnose MDR and XDR-TB among presumptive tuberculosis patients. Results showed a high rate of rifampicin resistance and the presence of extensively drug-resistant tuberculosis in new patients, highlighting the need for further studies on TB drug resistance in the country.
ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS
(2021)
Review
Microbiology
Christopher G. Shield, Benjamin M. C. Swift, Timothy D. McHugh, Rebekah M. Dedrick, Graham F. Hatfull, Giovanni Satta
Summary: Mycobacterium tuberculosis and other non-tuberculous mycobacteria cause various infections, with difficulties in diagnosis and treatment. Bacteriophages have emerged as potential new technologies for diagnosis and treatment in recent years.
Article
Microbiology
Dimitrios Evangelopoulos, Carolyn M. Shoen, Isobella Honeyborne, Simon Clark, Ann Williams, Galina V. Mukamolova, Michael H. Cynamon, Timothy D. McHugh
Summary: We report the adaptation of a culture-free assay for counting the bacterial load in animal tissues, which can accurately detect bacteria that cannot grow on solid culture media. This assay has the potential to decrease the readout time of data acquisition from animal experiments and could be a valuable tool for tuberculosis drug discovery and development.
Article
Infectious Diseases
Arundhati Maitra, Priya Solanki, Zahra Sadouki, Timothy D. McHugh, Frank Kloprogge
Summary: Mycobacterial infections are challenging to treat, with limited options due to antibiotic resistance. Drug development is resource-intensive and high-risk, leading to market failure in antimicrobial drug discovery programs. The hollow fibre infection model (HFIM) is an effective tool for evaluating the efficacy of drug combinations.
Article
Infectious Diseases
Anna Bateson, Julio Ortiz Canseco, Timothy D. McHugh, Adam A. Witney, Silke Feuerriegel, Matthias Merker, Thomas A. Kohl, Christian Utpatel, Stefan Niemann, Sonke Andres, Katharina Kranzer, Florian P. Maurer, Arash Ghodousi, Emanuele Borroni, Daniela Maria Cirillo, Maria Wijkander, Juan C. Toro, Ramona Groenheit, Jim Werngren, Diana Machado, Miguel Viveiros, Robin M. Warren, Frederick Sirgel, Anzaan Dippenaar, Claudio U. Koeser, Eugene Sun, Juliano Timm
Summary: The study reveals ancient differences in susceptibility to pretomanid among different lineages of Mycobacterium tuberculosis complex (MTBC) and recent emergence of resistance. The findings highlight the significance of considering global diversity of MTBC in clinical drug development and defining breakpoints for antimicrobial susceptibility testing.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Medicine, General & Internal
Fakhur Uddin, Muhammad Sohail, Qurban Hussain Shaikh, Mir Tahir Hussain, Kerry Roulston, Timothy Daniel McHugh
Summary: Pseudomonas balearica, a saprophyte found in marshy and marine habitats, was identified using MALDI-TOF-MS and 16S rDNA sequence from a patient admitted to an intensive care unit. The isolate was found to be resistant to multiple antibiotics and can be a potential source for the horizontal transfer of certain genes. Its pathogenesis remains to be understood.
JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
(2022)
Article
Microbiology
Hasmik Margaryan, Dimitrios D. Evangelopoulos, Leticia Muraro Wildner, Timothy D. McHugh
Summary: Combination therapy has shown some success in limiting drug-resistant tuberculosis by simultaneously acting on different targets and pathways. It also helps in shortening the duration of therapy. Systems biology approaches are used to analyze the cellular processes of mycobacteria and identify the networks and pathways associated with M. tuberculosis infection and survival. However, the most predictive combination of preclinical models for assessing clinical treatment efficacy remains unclear.
Correction
Microbiology
Muhammad Hayat Haider, Timothy D. McHugh, Kerry Roulston, Lia Barbara Arruda, Zahra Sadouki, Saba Riaz
ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS
(2022)
Article
Medicine, General & Internal
Bern-Thomas Nyang'wa, Catherine Berry, Emil Kazounis, Ilaria Motta, Nargiza Parpieva, Zinaida Tigay, Varvara Solodovnikova, Irina Liverko, Ronelle Moodliar, Matthew Dodd, Nosipho Ngubane, Mohammed Rassool, Timothy D. McHugh, Melvin Spigelman, David A. J. Moore, Koert Ritmeijer, Philipp du Cros, Katherine Fielding, TB-PRACTECAL Study Collaborators
Summary: The study aimed to evaluate the efficacy and safety of three all-oral regimens for the treatment of rifampin-resistant tuberculosis. The results showed that a 24-week all-oral regimen was noninferior to standard care and had fewer side effects.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Multidisciplinary Sciences
Frank Kloprogge, Julio Ortiz Canseco, Lynette Phee, Zahra Sadouki, Karin Kipper, Adam A. Witney, Neil Stoker, Timothy D. McHugh
Summary: This study investigated the concentration dependency of isoniazid-rifampicin resistance emergence and found that rifampicin resistance is the result of non-specific mechanisms, while part of isoniazid resistance is associated with the accumulation of specific SNPs. Additionally, the study showed that resistance does not emerge in concentration-time profiles mimicking the granuloma.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Linzy Elton, Sandeep Kasaragod, Helen Donoghue, Hussain A. Safar, Priscilla Amankwah, Alimuddin Zumla, Adam A. Witney, Timothy D. McHugh
Summary: The BCG vaccine has been used for tuberculosis prevention for over a century, but its efficacy varies across different regions. Genetic differences in BCG strains may contribute to this variation.
MICROBIAL GENOMICS
(2023)