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
Multidisciplinary Sciences
Yuchen Wang, Yuting Tang, Chen Lin, Junli Zhang, Juntao Mai, Jun Jiang, Xiaoxiao Gao, Yao Li, Guoping Zhao, Lu Zhang, Jun Liu
Summary: The ESX-4 system in Mycobacterium marinum does not secrete its cognate substrates, but the deletion of eccC4, an essential component of ESX-4, resulted in elevated secretion of protein substrates of ESX-1 and ESX-5, leading to enhanced phagocytosis by macrophages.
Article
Multidisciplinary Sciences
Katherine S. H. Beckham, Christina Ritter, Grzegorz Chojnowski, Daniel S. Ziemianowicz, Edukondalu Mullapudi, Mandy Rettel, Mikhail M. Savitski, Simon A. Mortensen, Jan Kosinski, Matthias Wilmanns
Summary: The ESX-5 type VII secretion system is a membrane-spanning protein complex crucial to the virulence of mycobacterial pathogens. The high-resolution structure of the 2.1-megadalton ESX-5 core complex reveals a dynamic, secretion-competent conformation of the pore with flexibility for accommodating targeted protein secretion, suggesting that a highly dynamic state of the pore may be a fundamental principle of bacterial secretion machineries.
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
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
Microbiology
Angel Rivera-Calzada, Nikolaos Famelis, Oscar Llorca, Sebastian Geibel
Summary: Type VII secretion systems play a crucial role in the secretion of effector proteins in both pathogenic and non-pathogenic mycobacteria. Recent advances in understanding the structure and biology of T7SSs have shed light on their inner workings and provided new insights for targeting the deadly human pathogen M. tuberculosis.
NATURE REVIEWS MICROBIOLOGY
(2021)
Review
Microbiology
Lisa Bowman, Tracy Palmer
Summary: The T7SS of Staphylococcus aureus plays a crucial role in virulence in disease models and intraspecies competition, with its genes located at the ess locus encoding multiple substrate recognition proteins. T7SS is widely conserved across staphylococci, encoding various toxin and immunity genes, while genomic islands encoding multiple immunity proteins in species lacking T7SS suggest a significant role for the secretion system in bacterial antagonism.
ANNUAL REVIEW OF MICROBIOLOGY, VOL 75, 2021
(2021)
Article
Immunology
Christopher J. Alteri, Nora Rios-Sarabia, Miguel A. De la Cruz, Jorge A. Gonzalez-y-Merchand, Jorge Soria-Bustos, Carmen Maldonado-Bernal, Maria L. Cedillo, Jorge A. Yanez-Santos, Ygnacio Martinez-Laguna, Javier Torres, Richard L. Friedman, Jorge A. Giron, Miguel A. Ares
Summary: The study found that expression of tad/flp genes was significantly higher in the stationary phase compared to other growth phases, indicating that the bacteria do not require type IV pili during dormancy. Elevated gene expression levels were recorded when the bacteria were in contact with macrophages or epithelial cells for 4 hours compared to bacteria propagated alone. Antibody detection showed the presence of Flp pili on intra- and extracellular bacteria infecting eukaryotic cells.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Chemistry, Medicinal
Kylee Drever, Ze Long Lim, Slim Zriba, Jeffrey M. Chen
Summary: This study provides the first evidence of the importance of mycobacterial proteostasis to ESX-1 secretion system and identifies novel vulnerabilities in the ESX-1 system for potential anti-TB drug targets.
ACS INFECTIOUS DISEASES
(2021)
Article
Microbiology
Glennon Bythrow, Manal F. Farhat, Keith Levendosky, Poornima Mohandas, Gabrielle A. Germain, Barney Yoo, Luis E. N. Quadri
Summary: The opportunistic pathogen Mab is associated with chronic pulmonary disease. Understanding its biology can lead to better therapeutics. This study reveals a functional link between the ESX-3 secretion system and an iron uptake system, and identifies a potentially pathogenic siderophore.
Review
Immunology
Michal Bar-Oz, Michal Meir, Daniel Barkan
Summary: Non-tuberculous mycobacteria (NTM) are a group of diverse organisms that are increasingly recognized as pathogens. Among NTMs, Mycobacterium abscessus (Mabs) causes severe and difficult to treat infections. The knowledge of the mechanisms of virulence in Mabs is limited compared to that in M. tuberculosis (Mtb). This review provides a framework and knowledge base for researchers interested in studying the secretion of virulence-associated molecules in Mabs.
FRONTIERS IN IMMUNOLOGY
(2022)
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
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.
Review
Veterinary Sciences
Laura Hunter, Ines Ruedas-Torres, Irene Agullo-Ros, Emma Rayner, Francisco J. Salguero
Summary: Research on human tuberculosis is limited due to the availability of human tissues, making animal models crucial for understanding the disease's progression and evaluating new therapies. This review examines the pulmonary pathology induced by tuberculosis bacteria in different animal models and compares them to human pulmonary tuberculosis. Although the models share some histopathological features with human tuberculosis, further research is needed to establish the most appropriate model and standard characterization of pulmonary lesions.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Article
Multidisciplinary Sciences
Uday Tak, Terje Dokland, Michael Niederweis
Summary: The tuberculosis necrotizing toxin (TNT) is secreted by Mycobacterium tuberculosis to kill host cells, with proteins EsxE and EsxF forming membrane-spanning hetero-oligomeric pores that are essential for TNT secretion.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Maroeska J. Burggraaf, Lisette Waanders, Mariska Verlaan, Janneke Maaskant, Diane Houben, Joen Luirink, Wilbert Bitter, Coen Kuijl, Carla F. M. Molthoff
Summary: By labeling the bacterial surface with adhesion protein FimH, the binding of Ty21a to bladder tumor cells and bladder wall was significantly improved, resulting in a modest increase in median survival in a single bladder cancer mouse study.
Article
Microbiology
Vien Q. T. Ho, Theo Verboom, Mark K. Rong, Eva Habjan, Wilbert Bitter, Alexander Speer
Summary: Screening for antituberculosis compounds using Mycobacterium tuberculosis is costly and time-consuming due to the requirement of biosafety level 3 facilities. Mycobacterium marinum, a close genetic relative, shows promise as a model for drug screening, with genetic differences in drug susceptibility compared to M. tuberculosis. By overexpressing drug activators EthA and KatG, M. marinum strains demonstrated increased susceptibility to key antituberculosis drugs and potential novel compounds from the TB Alliance library, making them valuable tools for drug discovery.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
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
Biology
Michaela Wenzel, Marien P. Dekker, Biwen Wang, Maroeska J. Burggraaf, Wilbert Bitter, Jan R. T. van Weering, Leendert W. Hamoen
Summary: The flat embedding method developed by Wenzel et al. for TEM allows for the observation of a large number of longitudinally cut cells in microbiological samples. By applying this technique to various bacteria, they discovered unexpected membrane deformations in B. subtilis cells treated with tetracycline, which was not caused by ribosome inhibition but rather a secondary antibacterial activity of the antibiotic. This new method increases the fraction of appropriately orientated cells per image, facilitating the quantification of cell morphology.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Catalin M. Bunduc, Dirk Fahrenkamp, Jiri Wald, Roy Ummels, Wilbert Bitter, Edith N. G. Houben, Thomas C. Marlovits
Summary: The T7SS inner-membrane complex of Mycobacterium tuberculosis is unique in structure and essential for virulence, with the protease MycP(5) playing a crucial role in complex integrity. This study reveals a previously undescribed mechanism of protein transport and provides a potential target for drug development against this major human pathogen.
Article
Microbiology
Sanne van der Niet, Maaike van Zon, Karin de Punder, Anita Grootemaat, Sofie Rutten, Simone J. C. F. M. Moorlag, Diane Houben, Astrid M. van der Sar, Wilbert Bitter, Roland Brosch, Rogelio Hernandez Pando, Maria T. Pena, Peter J. Peters, Eric A. Reits, Katrin D. Mayer-Barber, Nicole N. van der Wel
Summary: Mycobacterium tuberculosis infections claim more than a million lives each year, with translocation to the cytosol being a crucial pathogenicity factor. In vivo, mycobacteria translocate mainly when host immunity is compromised. The control of cytosolic mycobacteria is mediated by adaptive immune responses and IL-1R1.
Article
Immunology
James Gallant, Tiaan Heunis, Caroline Beltran, Karin Schildermans, Sven Bruijns, Inge Mertens, Wilbert Bitter, Samantha L. Sampson
Summary: Study found that PPE38-deficient M. tuberculosis resulted in decreased pro-inflammatory response in macrophages compared to wild type bacteria. This phenomenon was associated with the activation of the RelB/p50 pathway, indicating a molecular mechanism by which PPE38 controls macrophage responses through NF-kB signaling.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Infectious Diseases
Gina K. Schouten, Felix M. Paulussen, Oscar P. Kuipers, Wilbert Bitter, Tom N. Grossmann, Peter van Ulsen
Summary: The rising incidence of multidrug resistance in Gram-negative bacteria calls for novel treatment options. One promising approach is the combination of antibiotics with antimicrobial peptides. However, the use of such peptides is challenging due to their susceptibility to proteolytic degradation. This study demonstrates that the introduction of a hydrocarbon staple can enhance the stability and therapeutic potential of antimicrobial peptides without increasing their toxicity or hemolytic activity.
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
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.
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
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)
