Article
Immunology
Thomas C. Morris, Clive J. Hoggart, Novel N. Chegou, Martin Kidd, Tolu Oni, Rene Goliath, Katalin A. Wilkinson, Hazel M. Dockrell, Lifted Sichali, Louis Banda, Amelia C. Crampin, Neil French, Gerhard Walzl, Michael Levin, Robert J. Wilkinson, Melissa S. Hamilton
Summary: A study evaluated serum protein biomarkers discovered in primary care cohorts from Africa reapplied to patients from secondary care, discovering a nine-protein signature to distinguish tuberculosis from other diseases. This signature showed high sensitivity and specificity, indicating the potential for serum proteins as point-of-care screening tests for TB in African hospitals. Additionally, complement factor H was identified as a new biomarker for such signatures.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Clare M. Smith, Richard E. Baker, Megan K. Proulx, Bibhuti B. Mishra, Jarukit E. Long, Sae Woong Park, Ha-Na Lee, Michael C. Kiritsy, Michelle M. Bellerose, Andrew J. Olive, Kenan C. Murphy, Kadamba Papavinasasundaram, Frederick J. Boehm, Charlotte J. Reames, Rachel K. Meade, Brea K. Hampton, Colton L. Linnertz, Ginger D. Shaw, Pablo Hock, Timothy A. Bell, Sabine Ehrt, Dirk Schnappinger, Fernando Pardo-Manuel de Villena, Martin T. Ferris, Thomas R. Ioerger, Christopher M. Sassetti, Bavesh D. Kana
Summary: This study utilizes a genetically diverse Collaborative Cross mouse panel and a library of Mtb mutants to investigate the relationship between bacterial genetic requirements and host genetics and immunity. Global analysis reveals that many virulence pathways are only required in specific host microenvironments, and a large portion of the pathogen's genome has been maintained for fitness in a diverse population. The study identifies genetic variants across the mouse genome that are associated with both immunological and bacterial traits, providing a unique population for studying specific host-pathogen genetic interactions that influence pathogenesis.
Review
Immunology
Oyindamola O. Adefisayo, Erin R. Curtis, Clare M. Smith
Summary: The causative agent of tuberculosis, Mycobacterium tuberculosis, has evolved unique phenotypic traits through selective pressures within host cells, contributing to its evolutionary success. Understanding the genetic repertoire used by Mtb to drive virulence and host immune evasion is crucial but remains a challenge. In this review, the employment of mycobacterial genetic tools to study the host-pathogen interaction is evaluated, with a focus on the murine model.
INFECTION AND IMMUNITY
(2023)
Review
Microbiology
Lindsey Dzierozynski, Jessica Queen, Cynthia L. Sears
Summary: This commentary discusses the influence of host genetics on the microbiome and highlights the need for mechanistic experimental studies to understand the interplay between host genes and the microbiome.
CELL HOST & MICROBE
(2023)
Editorial Material
Multidisciplinary Sciences
Louise Humphrey, Abdeljalil Bouzouggar
Summary: Genomic data from bones and teeth found at archaeological sites across Morocco reveal a more intricate spread of Neolithic farmers and pastoralists into northwest Africa than previously believed.
Editorial Material
Biochemistry & Molecular Biology
Madison A. Youngblom, Caitlin S. Pepperell
Summary: In this study, Saelens et al. uncover a novel function of mycobacterial Type VII secretion systems in manipulating host cell migration. The absence of this function in a substantial proportion of global TB cases raises questions about its role in pathoadaptation of Mycobacterium tuberculosis, providing new insights for further investigations.
Review
Immunology
Khushboo Borah, Ye Xu, Johnjoe McFadden
Summary: Tuberculosis is a devastating infectious disease that kills over a million people annually, with increasing challenges of multi and extensively drug resistant strains. Host-pathogen interactions, metabolic cross talk, and advancements in systems-based omic technologies play critical roles in TB research and offer promising interventions for anti-TB therapies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Microbiology
Eui-Kwon Jeong, Hyo-Ji Lee, Yu-Jin Jung
Summary: Tuberculosis (TB) is a major cause of death globally and poses a continuous threat to public health. Conventional TB treatment is associated with long-term treatment regimens and side effects. With the emergence of drug-resistant TB, there is an urgent need for the development of new treatment strategies. This article introduces host-directed therapy (HDT) as an alternative approach that modulates host immune responses to effectively treat TB.
Article
Neurosciences
Anna I. Dunigan, David P. Olson, Aaron G. Roseberry
Summary: Studies suggest that VTA MC3R neurons play a crucial role in food intake regulation, with significant sex differences observed in behavior, where opposing changes in neuronal activity in male and female mice lead to similar changes in behavior.
Article
Infectious Diseases
Thomas Nyirenda, Moses Bockarie, Shingai Machingaidze, Michelle Nderu, Michelle Singh, Nuraan Fakier, Jean-Marie Habarugira, Pauline Beattie, Lara Pandya, Dominika Jajkowicz, Yazdan Yazdanpanah, Catherine Hankins, Michael Makanga
Summary: Global research collaboration is essential for delivering impactful and sustainable research for the global good. The EDCTP model focuses on capacity development in clinical trials and product-focused implementation research, emphasizing the importance of long-term perspective, a system-wide approach, and local ownership.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Review
Biochemistry & Molecular Biology
Rachana R. Borkute, Soeren Woelke, Gang Pei, Anca Dorhoi
Summary: Neutrophils play a complex role in tuberculosis, with both beneficial and detrimental effects on disease outcomes. Recent studies have revealed the phenotypic heterogeneity of neutrophils and their interactions with other cells in TB pathophysiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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)
Review
Public, Environmental & Occupational Health
Prince Asare, Adwoa Asante-Poku, Stephen Osei-Wusu, Isaac Darko Otchere, Dorothy Yeboah-Manu
Summary: Tuberculosis remains a global health problem, particularly in West Africa where unique epidemiology and geographical restrictions of M. africanum add complexity to the burden of TB. Challenges such as low case detection, poor treatment adherence, and drug resistance highlight the need for sensitive tools and genomic epidemiology research.
FRONTIERS IN PUBLIC HEALTH
(2021)
Article
Endocrinology & Metabolism
Xiaozhu Wang, Song Xue, Xiaowei Lei, Wenqi Song, Lei Li, Xuan Li, Yanbin Fu, Cong Zhang, Hailin Zhang, Yao Luo, Meng Wang, Gufa Lin, Chao Zhang, Jing Guo
Summary: In this study, the researchers investigated the role of MRAP2 in the regulation of central melanocortin signaling in the Mexican axolotl. They found that the conservation of axolotl mc3r and mc4r is higher than mrap2, and the axolotl MC3R/MC4R is closer to their counterparts in the clawed frog. The researchers also confirmed the co-expression and functional complex formation of axolotl MC3R/MC4R and MRAP2 on the plasma membrane.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lara C. Linnemann, Ulrich E. Schaible, Tobias K. Dallenga
Summary: Host-directed therapies targeting immune pathways associated with pathogenesis in tuberculosis may improve disease and bacterial clearance. However, the efficacy of these therapies may vary between human and mouse models, as mouse models may not fully resemble the pathomechanisms of human tuberculosis. In this study, inhibition of myeloperoxidase (MPO) failed to prevent necrosis in mouse neutrophils infected with M. tuberculosis, in contrast to the previous findings in human neutrophils. These results suggest that murine infection models may not be suitable for evaluating host-directed therapies targeting neutrophils.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Chemistry, Multidisciplinary
Christian Lienhardt, Mario C. Raviglione
APPLIED SCIENCES-BASEL
(2020)
Review
Biochemistry & Molecular Biology
Uwe Richter, Robert McFarland, Robert W. Taylor, Sarah J. Pickett
Summary: Mitochondrial diseases are a group of clinically and genetically heterogeneous disorders caused by pathogenic variants in either the nuclear or mitochondrial genome. This review focuses on the most common pathogenic mt-tRNA variants, exploring their clinical manifestations, molecular pathologies, and potential molecular mechanisms of disease. Additionally, the role of mitochondrial-nuclear crosstalk in the manifestation of mt-tRNA-associated disease and the potential for developing treatment options are discussed.
Article
Neurosciences
Chun Chen, David McDonald, Alasdair Blain, Ashwin Sachdeva, Laura Bone, Anna L. M. Smith, Charlotte Warren, Sarah J. Pickett, Gavin Hudson, Andrew Filby, Amy E. Vincent, Doug M. Turnbull, Amy K. Reeve
Summary: This study utilized imaging mass cytometry to analyze the proteomic profiles of mitochondrial complexes in neurons from Parkinson's disease patients. The results revealed a widespread decrease in expression of all mitochondrial complexes in Parkinson's neurons, with a more severe decrease in mitochondrial disease neurons. Furthermore, the combination of affected complexes varied between the two groups, suggesting a potential compensatory increase in mitochondrial mass as a response to dysfunction.
NPJ PARKINSONS DISEASE
(2021)
Article
Critical Care Medicine
Maroussia Roelens, Giovanni Battista Migliori, Liudmila Rozanova, Janne Estill, Jonathon R. Campbell, J. Peter Cegielski, Simon Tiberi, Domingo Palmero, Greg J. Fox, Lorenzo Guglielmetti, Giovanni Sotgiu, James C. M. Brust, Didi Bang, Christian Lienhardt, Christoph Lange, Dick Menzies, Olivia Keiser, Mario Raviglione
Summary: The study supports a new definition of XDR-TB as MDR-TB with additional resistance to FQ plus bedaquiline and/or linezolid, which helps assess the adequacy of this definition for surveillance and treatment choice.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Review
Medicine, Research & Experimental
N. K. Hills, J. Lyimo, P. Nahid, R. M. Savic, C. Lienhardt, P. P. J. Phillips
Summary: This study reviewed 31 clinical trials and found heterogeneous outcome definitions, highlighting the need to establish clearer specification and move towards universal standardization of outcomes across pulmonary TB trials. The ICH E9 (R1) addendum provides guidelines for achieving this goal.
Review
Microbiology
Mark S. Butler, Valeria Gigante, Hatim Sati, Sarah Paulin, Laila Al-Sulaiman, John H. Rex, Prabhavathi Fernandes, Cesar A. Arias, Mical Paul, Guy E. Thwaites, Lloyd Czaplewski, Richard A. Alm, Christian Lienhardt, Melvin Spigelman, Lynn L. Silver, Norio Ohmagari, Roman Kozlov, Stephan Harbarth, Peter Beyer
Summary: There is an urgent global need for new strategies and drugs to control and treat multidrug-resistant bacterial infections. The World Health Organization has identified antibiotic-resistant priority pathogens and critically analyzed the antibacterial clinical pipeline. While new antibacterial drugs are being developed, there is still a lack of clinically differentiated agents.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Editorial Material
Immunology
Sonali Kochhar, Draurio Barreira, Pauline Beattie, Marco Cavaleri, Alejandro Cravioto, Mike W. Frick, Ann M. Ginsberg, Ian Hudson, David C. Kaslow, Sherry Kurtz, Christian Lienhardt, Shabir A. Madhi, Christopher Morgan, Yalda Momeni, Deepali Patel, Helen Rees, Taryn Rogalski-Salter, Alexander Schmidt, Boitumelo Semete-Makokotlela, Gerald Voss, Richard G. White, Matteo Zignol, Birgitte Giersing
Summary: Currently, there is a lack of formal mechanisms or systematic approaches to provide vaccine developers with anticipated evidence to support global policy recommendations. To address this issue, the World Health Organization (WHO) is evaluating a new strategic alignment tool called Evidence Considerations for Vaccine Policy (ECVP). The aim of ECVPs is to bridge the gap in evidence needs and reduce the risk of delays between vaccine recommendation and use.
Letter
Microbiology
Mark S. Butler, Valeria Gigante, Hatim Sati, Sarah Paulin, Laila Al-Sulaiman, John H. Rex, Prabhavathi Fernandes, Cesar A. Arias, Mical Paul, Guy E. Thwaites, Lloyd Czaplewski, Richard A. Alm, Christian Lienhardt, Melvin Spigelman, Lynn L. Silver, Norio Ohmagari, Roman Kozlov, Stephan Harbarth, Peter Beyer
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Medicine, General & Internal
Juan F. Vesga, Christian Lienhardt, Placide Nsengiyumva, Jonathon R. Campbell, Olivia Oxlade, Saskia den Boon, Dennis Falzon, Kevin Schwartzman, Gavin Churchyard, Nimalan Arinaminpathy
Summary: This study analyzed the five most important regimen properties influencing the epidemiological impact of preventive tuberculosis treatment regimens, finding that efficacy is the most important predictor, with ease-of-adherence playing a significant secondary role. These results are consistent across different country settings and provide guidance for the further development of future treatment regimens.
Article
Infectious Diseases
S. Den Boon, C. Lienhardt, M. Zignol, K. Schwartzman, N. Arinaminpathy, J. R. Campbell, P. Nahid, M. Penazzato, D. Menzies, J. F. Vesga, O. Oxlade, G. Churchyard, C. S. Merle, T. Kasaeva, D. Falzon
Summary: The WHO has developed target product profiles to guide the development of new tuberculosis treatment regimens. A technical consultation group identified attributes with the greatest potential impact for patients and populations, categorizing them as priority or desirable. The study identified nine priority attributes and four desirable attributes.
INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
(2022)
Article
Cell Biology
Sarah J. Pickett, Dasha Deen, Angela Pyle, Mauro Santibanez-Koref, Gavin Hudson
Summary: Interactions between nuclear and mitochondrial genomes play a critical role in the function of eukaryotic cells. A study investigating the frequencies of combinations of nuclear and mitochondrial SNP alleles in healthy individuals and Parkinson's disease patients identified some combinations that significantly affect the risk of the disease. These findings provide new insights into the impact of genetic background on disease susceptibility.
Article
Biochemistry & Molecular Biology
Melissa Franco, Sarah J. Pickett, Zoe Fleischmann, Mark Khrapko, Auden Cote-L'Heureux, Dylan Aidlen, David Stein, Natasha Markuzon, Konstantin Popadin, Maxim Braverman, Dori C. Woods, Jonathan L. Tilly, Doug M. Turnbull, Konstantin Khrapko
Summary: The A-to-G point mutation at position 3243 in the human mitochondrial genome (m.3243A > G) is the most common pathogenic mtDNA variant responsible for disease in humans. It is widely accepted that m.3243A > G levels decrease with age in blood, and a 2% annual decline correction is often applied. However, recent data suggest that the dynamics of m.3243A > G are more complex and depend on the mutation level in blood in a biphasic way. This biphasic approach can greatly improve the accuracy of modeling changes in mtDNA mutation frequencies.
HUMAN MOLECULAR GENETICS
(2022)
Article
Medicine, General & Internal
Ntwali Placide Nsengiyumva, Jonathon R. Campbell, Olivia Oxlade, Juan F. Vesga, Christian Lienhardt, Anete Trajman, Dennis Falzon, Saskia Den Boon, Nimalan Arinaminpathy, Kevin Schwartzman
Summary: This study analyzed the cost-effectiveness of scaling up tuberculosis preventive treatment regimens in Brazil and South Africa. The results showed that expanding the use of these regimens would significantly improve the effectiveness of tuberculosis prevention and treatment and would be cost-effective or cost-saving.
Review
Public, Environmental & Occupational Health
Leonardo Martinez, Olivia Cords, Qiao Liu, Carlos Acuna-Villaorduna, Maryline Bonnet, Greg J. Fox, Anna Cristina C. Carvalho, Pei-Chun Chan, Julio Croda, Philip C. Hill, Elisa Lopez-Varela, Simon Donkor, Katherine Fielding, Stephen M. Graham, Marcos A. Espinal, Beate Kampmann, Arthur Reingold, Helena Huerga, Julian A. Villalba, Louis Grandjean, Giovanni Sotgiu, Uzochukwu Egere, Sarman Singh, Limei Zhu, Christian Lienhardt, Justin T. Denholm, James A. Seddon, Christopher C. Whalen, Alberto L. Garcia-Basteiro, Rina Triasih, Cheng Chen, Jitendra Singh, Li-Min Huang, Surendra Sharma, Djohar Hannoun, Helena Del Corral, Anna M. Mandalakas, LaShaunda L. Malone, Du-Lin Ling, Afranio Kritski, Catherine M. Stein, Richa Vashishtha, Fadila Boulahbal, Chi-Tai Fang, W. Henry Boom, Eduardo Martins Netto, Antonio Carlos Lemos, Anneke C. Hesseling, Alexander Kay, Edward C. Jones-Lopez, C. Robert Horsburgh, Christoph Lange, Jason R. Andrews
Summary: This study aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis development and mortality. Through a systematic review and meta-analysis, the effectiveness of BCG vaccination was found to be significant in preventing tuberculosis in children younger than 5 years, but ineffective in adolescents and adults.
LANCET GLOBAL HEALTH
(2022)
Article
Immunology
Christian Ducrot, Alexandre Hobeika, Christian Lienhardt, Barbara Wieland, Charlotte Dehays, Alexis Delabouglise, Marion Bordier, Flavie Goutard, Ekta Patel, Muriel Figuie, Marisa Peyre, Arshnee Moodley, Francois Roger
Summary: Although Africa has the lowest antimicrobial usage in animals globally, there is a high prevalence of antimicrobial resistance in foodborne pathogens from animals. Farmers lack knowledge and misuse antimicrobials, posing a serious public health threat. Policy interventions should be tailored to address the challenges faced by family farmers in Africa and provide innovative measures to tackle antimicrobial resistance.
EMERGING INFECTIOUS DISEASES
(2021)
