Article
Microbiology
Marion Lagune, Vincent Le Moigne, Matt D. Johansen, Flor Vasquez Sotomayor, Wassim Daher, Cecile Petit, Gina Cosentino, Laura Paulowski, Thomas Gutsmann, Matthias Wilmanns, Florian P. Maurer, Jean-Louis Herrmann, Fabienne Girard-Misguich, Laurent Kremer
Summary: ESX type VII secretion systems play an important role in pathogenicity, nutrient uptake and conjugation in mycobacteria. EsxU and EsxT are substrates of ESX-4 and form a stable heterodimer that permeabilizes artificial membranes. Deletion of the esxUT genes increases the virulence of M. abscessus in animal models.
Article
Microbiology
B. Izquierdo Lafuente, R. Ummels, C. Kuijl, W. Bitter, A. Speer
Summary: CpnT, a potent secreted toxin of Mycobacterium tuberculosis, is exclusively secreted by the ESX-5 system in bacterial culture but relies on intact ESX-1, ESX-4, and ESX-5 systems during infection studies. This highlights the intricate interplay of three different secretion systems in secreting one substrate during infection.
Article
Microbiology
Merel P. M. Damen, Aniek S. Meijers, Esther M. Keizer, Sander R. Piersma, Connie R. Jimenez, Coenraad P. Kuijl, Wilbert Bitter, Edith N. G. Houben
Summary: Pathogenic mycobacteria utilize the ESX-1 secretion system to mediate intracellular survival, but determining the responsible ESX-1 substrate is challenging due to complex secretion dependencies. This study reveals the critical role of the ESX-1 substrate PPE68 in mediating the secretion of ESX-1 substrates in Mycobacterium marinum, providing insights into the functional understanding of T7SSs and the virulence of Mycobacterium tuberculosis.
Article
Chemistry, Multidisciplinary
Jianping Lu, Jiali Ding, Binbin Chu, Chen Ji, Qian Zhang, Yanan Xu, Bin Song, Houyu Wang, Yao He
Summary: We found that dead Escherichia coli K1 (EC-K1) can safely penetrate the blood-brain barrier (BBB), and developed a drug delivery system using dead EC-K1, which retain the intact structure and chemotaxis of live EC-K1 but lose their pathogenicity. The dead bacteria carry therapeutics and bypass the BBB, delivering higher doses into the brain than free therapeutics. This strategy enables the therapy of bacterial meningitis and glioblastoma in mice.
Article
Biochemistry & Molecular Biology
Carlos Sanchez-Garibay, Citlaltepetl Salinas-Lara, Marcos Artemio Gomez-Lopez, Luis O. Soto-Rojas, Nidia Karen Castillon-Benavides, Omar Jorge Castillon-Benavides, Maria Elena Hernandez-Campos, Rogelio Hernandez-Pando, Brenda Marquina-Castillo, Manuel Alejandro Flores-Barrada, Jose Alberto Choreno-Parra, Juan Carlos Leon-Contreras, Martha Lilia Tena-Suck, Dulce Adriana Mata-Espinosa, Porfirio Nava, Jessica Medina-Mendoza, Cesar Augusto Rodriguez-Balderas
Summary: This study evaluated the morphostructural and molecular integrity of CNS barriers and found that Mycobacterium tuberculosis can disrupt the BCSFB. The ability of different strains to cause CNS disease may be linked to their capacity to disrupt these barriers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Public, Environmental & Occupational Health
Abhishek Shridhar, Ravindra Kumar Garg, Imran Rizvi, Mili Jain, Wahid Ali, Hardeep Singh Malhotra, Neeraj Kumar, Praveen Kumar Sharma, Rajesh Verma, Ravi Uniyal, Shweta Pandey
Summary: This study evaluated the proportion of underlying primary immunodeficiency in patients with tuberculous meningitis and its impact on the outcome. The results showed that absolute lymphocyte count and CD4+ T-cell count were lower in tuberculous meningitis cases, and higher serum IgG levels may be associated with a poor outcome.
JOURNAL OF INFECTION AND PUBLIC HEALTH
(2022)
Review
Microbiology
Robindra Basu Roy, Sabrina Bakeera-Kitaka, Chishala Chabala, Diana M. Gibb, Julie Huynh, Hilda Mujuru, Naveen Sankhyan, James A. Seddon, Suvasini Sharma, Varinder Singh, Eric Wobudeya, Suzanne T. Anderson
Summary: Children affected by tuberculous meningitis have complex needs that may not be fully addressed within current tuberculosis and meningitis programs. By applying the five pillars outlined in the global roadmap, specific goals and activities can be implemented to defeat TBM in children. Integration between meningitis and TB programs at both the WHO and national levels is crucial for addressing these needs effectively.
Article
Clinical Neurology
Karen du Preez, Helen E. Jenkins, Peter R. Donald, Regan S. Solomons, Stephen M. Graham, H. Simon Schaaf, Jeffrey R. Starke, Anneke C. Hesseling, James A. Seddon
Summary: Tuberculous meningitis (TBM) is a significant cause of illness and death in children with tuberculosis (TB), but there are currently no estimates of the global burden of pediatric TBM. Due to non-specific symptoms and limited diagnostic tests, children with TBM are often diagnosed late or not at all. Even with diagnosis and treatment, 20% of children with TBM still die and survivors often have significant neurological disabilities. Improved surveillance of pediatric TBM is crucial for prevention, early diagnosis, and improved care.
FRONTIERS IN NEUROLOGY
(2022)
Article
Immunology
Jaime Soria, Alfredo Chiappe, Jorge Gallardo, Joseph R. Zunt, Andres G. Lescano
Summary: The impact of treatment initiation timing on mortality was studied in adult hospitalized patients with confirmed tuberculous meningitis. The high mortality rate among these patients was associated with delay in treatment initiation, older age, HIV infection, and higher disease severity at admission.
OPEN FORUM INFECTIOUS DISEASES
(2021)
Review
Clinical Neurology
Kenneth Ssebambulidde, Jane Gakuru, Jayne Ellis, Fiona V. Cresswell, Nathan C. Bahr
Summary: Diagnosis of TBM remains challenging due to the limitations of current diagnostic methods. A combination of clinical factors and various investigations are utilized for diagnosis. Starting empiric therapy promptly is crucial for good outcomes in many cases.
FRONTIERS IN NEUROLOGY
(2022)
Article
Public, Environmental & Occupational Health
Mailing Huang, Yan Ma, Xinyu Ji, Hui Jiang, Fangchao Liu, Naihui Chu, Qi Li
Summary: This study aimed to identify the risk factors for tuberculous meningitis (TBM) among patients with tuberculosis (TB). A retrospective analysis was conducted on TB patients admitted to Beijing Chest Hospital between January 2012 and December 2019. The study found that being younger than 30, being a farmer, and having disseminated tuberculosis were identified as risk factors for TBM. Screening TB patients with these risk factors could aid in early detection of TBM.
FRONTIERS IN PUBLIC HEALTH
(2023)
Article
Clinical Neurology
Haiko Schurz, Brigitte Glanzmann, Nicholas Bowker, Ronald van Toorn, Regan Solomons, Johan Schoeman, Paul D. van Helden, Craig J. Kinnear, Eileen G. Hoal, Marlo Moeller
Summary: This study investigated the involvement of the host genome in susceptibility to tuberculous meningitis (TBM) using genotyping and sequencing methods. The results suggest that genes NOD2 and CYP4F2 may play important roles in the pathogenesis of TBM, while Centriolar Coiled-Coil Protein 110 (CCP110) may be associated with susceptibility to TBM.
FRONTIERS IN NEUROLOGY
(2022)
Review
Microbiology
Charles M. Manyelo, Regan S. Solomons, Gerhard Walz, Novel N. Cheyou
Summary: Tuberculous meningitis is a devastating form of tuberculosis with limited understanding of its immunology and pathogenesis. Further research is urgently needed to improve disease management and develop new therapeutic approaches.
JOURNAL OF CLINICAL MICROBIOLOGY
(2021)
Article
Microbiology
Navarat Panjasawatwong, Thanaporn Wattanakul, Richard M. Hoglund, Nguyen Duc Bang, Thomas Pouplin, Wichit Nosoongnoen, Vi Nguyen Ngo, Jeremy N. Day, Joel Tarning
Summary: This study investigated the population pharmacokinetics of isoniazid, rifampin, pyrazinamide, and ethambutol in Vietnamese children with TBM, recommended higher rifampin doses to achieve target exposure, and found that low rifampin plasma exposure was associated with an increased risk of neurological disability.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Medicine, General & Internal
Jayantee Kalita, Prakash C. Pandey, Ruchi Shukla, Rudrashish Haldar
Summary: Patients with tuberculous meningitis have prolonged fever response, and the expression of TNF-alpha gene can predict the duration of fever subsidence. Further studies are needed to explore the potential role of TNF-alpha-modifying drugs in tuberculous meningitis.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Ecology
Meggie Hudspith, Jasper M. de Goeij, Mischa Streekstra, Niklas A. Kornder, Jeremy Bougoure, Paul Guagliardo, Sara Campana, Nicole N. van der Wel, Gerard Muyzer, Laura Rix
Summary: The ability of organisms to combine autotrophy and heterotrophy gives rise to the successful nutritional strategy of mixotrophy. This study focuses on the contribution of photoautotrophy to the respiratory demand and carbon diet of the sponge Chondrilla caribensis in low-light environments. The findings suggest that photoautotrophy can provide an important supplemental source of carbon for sponges residing in low-light habitats.
Article
Cell Biology
Rosalie S. N. Linssen, Adithya Sridhar, Giulia Moreni, Nicole N. van der Wel, Job B. M. van Woensel, Katja C. Wolthers, Reinout A. Bem
Summary: Research using human airway epithelial cell cultures showed that in the context of RSV infection, NETs did not cause or exacerbate epithelial injury or inflammation.
Article
Multidisciplinary Sciences
Tania N. Darphorn, Belinda Koenders-van Sintanneland, Anita H. Grootemaat, Nicole van der Wel, Stanley J. Brul, Benno J. ter Kuile
Summary: Resistance plasmid transfer rates are influenced by various factors, including species specificity and the presence of pili connections. Having plasmids does not seem to affect the metabolic burden on the host strain. The formation of aggregates is facilitated by an increased number of pili connections between cells, leading to higher transfer rates.
Article
Biochemistry & Molecular Biology
Valentina E. Gomez-Mellado, Kam S. Ho-Mok, Vincent A. van der Mark, Nicole N. van der Wel, Anita E. Grootemaat, Arthur J. Verhoeven, Ronald P. J. Oude Elferink, Coen C. Paulusma
Summary: ATP8B1 plays a crucial role in the endolysosomal pathway in macrophages, affecting degradation in the phagocytic pathway, overacidification of the endolysosomal system, and accumulation of autophagosomes. These findings reveal a novel role for ATP8B1 in lysosomal fusion in macrophages.
CELL BIOCHEMISTRY AND FUNCTION
(2022)
Article
Microbiology
Rob J. M. Van Spanning, Qingtian Guan, Chrats Melkonian, James Gallant, Lubos Polerecky, Jean-Francois Flot, Bernd W. Brandt, Martin Braster, Paul Iturbe Espinoza, Joost W. Aerts, Marion M. Meima-Franke, Sander R. Piersma, Catalin M. Bunduc, Roy Ummels, Arnab Pain, Emily J. Fleming, Nicole N. Van der Wel, Vasile D. Gherman, Serban M. Sarbu, Paul L. E. Bodelier, Wilbert Bitter
Summary: A study has found a methanotrophic Mycobacterium within the Actinobacteria, a group of bacteria not previously known to grow on methane under aerobic conditions. This Mycobacterium, named Candidatus Mycobacterium methanotrophicum, is closely related to well-known pathogens like M. tuberculosis and M. leprae. Genomic and proteomic analyses showed that Candidatus M. methanotrophicum possesses all the necessary enzymes for aerobic growth on methane. Stable isotope probing confirmed that this bacterium can use methane as its sole carbon and energy source.
NATURE MICROBIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Edgar E. Nollet, Inez Duursma, Anastasiya Rozenbaum, Moritz Eggelbusch, Rob C. Wuest, Stephan A. C. Schoonvelde, Michelle Michels, Mark Jansen, Nicole N. van der Wel, Kenneth C. Bedi, Kenneth B. Margulies Jr, Jeff Nirschl, Diederik W. D. Kuster, Jolanda van der Velden
Summary: This study found that mitochondrial dysfunction is related to pathological remodelling in hypertrophic cardiomyopathy (HCM). In patients without genetic mutations, there is a stronger association between mitochondrial dysfunction and septal hypertrophy. The study also suggests that targeting mitochondria with specific drugs can restore mitochondrial function in HCM patients.
EUROPEAN HEART JOURNAL
(2023)
Article
Microbiology
Merel P. M. Damen, Aniek S. Meijers, Esther M. Keizer, Sander R. Piersma, Connie R. Jimenez, Coenraad P. Kuijl, Wilbert Bitter, Edith N. G. Houben
Summary: Pathogenic mycobacteria utilize the ESX-1 secretion system to mediate intracellular survival, but determining the responsible ESX-1 substrate is challenging due to complex secretion dependencies. This study reveals the critical role of the ESX-1 substrate PPE68 in mediating the secretion of ESX-1 substrates in Mycobacterium marinum, providing insights into the functional understanding of T7SSs and the virulence of Mycobacterium tuberculosis.
Article
Cell Biology
Kin Ki Jim, Rieza Aprianto, Rutger Koning, Arnau Domenech, Jun Kurushima, Diederik van de Beek, Christina M. J. E. Vandenbroucke-Grauls, Wilbert Bitter, Jan-Willem Veening
Summary: This study investigates the specific transcriptional responses of pneumolysin and identifies key pathways involved in early pneumococcal meningitis using an in vivo dual RNA sequencing approach. The study provides new insights into the interactions between the host and pathogen during the early phase of central nervous system infection.
Article
Biochemistry & Molecular Biology
Vien Q. T. Ho, Mark K. Rong, Eva Habjan, Samantha D. Bommer, Thang V. Pham, Sander R. Piersma, Wilbert Bitter, Eelco Ruijter, Alexander Speer
Summary: In this study, a 1,2,4-oxadiazole derivative was found to inhibit the secretion of active lipase LipY by the ESX-5 secretion system. Other ESX-5 substrates were even more abundantly secreted in the presence of several 1,2,4-oxadiazoles. These compounds significantly reduced bacterial burden in zebrafish models.
Review
Biochemistry & Molecular Biology
Chunyuan Yin, Amy C. C. Harms, Thomas Hankemeier, Alida Kindt, Elizabeth C. M. de Lange
Summary: Alzheimer's disease is an aging-related neurodegenerative disease that leads to progressive memory loss and cognitive decline. Understanding the pathogenesis and etiology of the disease is still limited, and there are no effective treatments available. Metabolomics offers a valuable approach to studying biochemical changes and discovering potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Lisette Waanders, Lieve E. H. van der Donk, Louis S. Ates, Janneke Maaskant, John L. van Hamme, Eric Eldering, Jaco A. C. van Bruggen, Joanne M. Rietveld, Wilbert Bitter, Teunis B. H. Geijtenbeek, Coenraad P. Kuijl
Summary: By expressing cGAS in Salmonella typhimurium, the STING pathway can be activated in vitro, leading to enhanced cytotoxic T-cell response and tumor cell killing. This suggests the potential of Salmonella typhimurium-cGAS in vitro and provides rationale for further in vivo research.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Public, Environmental & Occupational Health
Germari Kruger, Eduardus A. J. G. van der Borght, Martha T. Teijema, Marceline Tutu van Furth
Summary: Faith leaders and health care workers in South African communities play a crucial role in supporting the health of community members and people living with HIV. This study highlights the importance of collaboration between faith leaders and health care workers in combating HIV stigma, and calls for organized cooperation between faith communities and health care structures in future research and interventions.
AJAR-AFRICAN JOURNAL OF AIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Ilona van Alen, Mayra A. Aguirre Garcia, Janneke J. Maaskant, Coenraad P. Kuijl, Wilbert Bitter, Annemarie H. Meijer, Marcellus Ubbink
Summary: This study tested the activity of variants of the beta-lactamase enzyme BlaC from Mycobacterium tuberculosis under more physiological conditions and investigated their effectiveness in combination therapy with antibiotics and inhibitors using a zebrafish infection model. The results suggest that the zebrafish host is less sensitive to the combinatorial therapy, which is important for the future development of combination therapies to treat tuberculosis.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Melissa Bedard, Sanne van der Niet, Elliott M. Bernard, Gregory Babunovic, Tan-Yun Cheng, Beren Aylan, Anita E. Grootemaat, Sahadevan Raman, Laure Botella, Eri Ishikawa, Mary P. O'Sullivan, Jacob A. Mayfield, Seonadh O'Leary, Jeffrey Buter, Adriaan J. Minnaard, Sarah M. Fortune, Leon O. Murphy, Daniel S. Ory, Joseph Keane, Sho Yamasaki, Maximiliano G. Gutierrez, Nicole van der Wel, D. Branch Moody
Summary: Induction of lipid-laden foamy macrophages is a characteristic of tuberculosis (TB) and is caused by a terpenyl nucleoside shed from Mycobacterium tuberculosis. This shed nucleoside, known as 1-tuberculosinyladenosine (1-TbAd), blocks lysosomal maturation and autophagy, leading to lipid storage in M1 macrophages. Furthermore, 1-TbAd induces the storage of specific lipids and promotes the growth of M. tuberculosis, as well as mimicking the lipid storage patterns found in lysosomal storage diseases such as Gaucher's disease and Wolman's disease.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Microbiology
Anita E. Grootemaat, Niek Wiersma, Sanne van der Niet, Irene M. Schimmel, Sandrine Florquin, Eric A. Reits, Sara E. Miller, Nicole N. van der Wel
Summary: This study investigated the presence of SARS-CoV-2 viral proteins and particles in the kidneys of fatal COVID-19 patients and patients with kidney failure after recovering from SARS-CoV-2 infection. The study found accumulation of the viral nucleocapsid N protein in the kidney tubular epithelium of a patient with acute kidney failure, but no replication of the virus in the kidney.
MICROBIOLOGY SPECTRUM
(2023)