المؤلفون: Angela Rodgers, Maximiliano G. Gutierrez, Antony Fearns, Daniel J. Greenwood, Haibo Jiang

المصدر: PLoS Biology, Vol 18, Iss 12, p e3000879 (2020)
PLoS Biology
PLoS Biology, 18 (12)

مصطلحات موضوعية: Male, 0301 basic medicine, Fluorescence-lifetime imaging microscopy, Antibiotics, Cell, Antitubercular Agents, Pathology and Laboratory Medicine, Diagnostic Radiology, Mice, White Blood Cells, chemistry.chemical_compound, Animal Cells, Microscopy, Medicine and Health Sciences, Electron Microscopy, Diarylquinolines, Biology (General), Lung, Tomography, Mice, Inbred C3H, biology, Antimicrobials, Radiology and Imaging, General Neuroscience, Methods and Resources, Drugs, Pulmonary Imaging, 3. Good health, Actinobacteria, Intracellular Pathogens, medicine.anatomical_structure, Female, Scanning Electron Microscopy, Cellular Types, Pathogens, General Agricultural and Biological Sciences, Imaging Techniques, QH301-705.5, medicine.drug_class, Immune Cells, Immunology, 030106 microbiology, Neuroimaging, Microbial Sensitivity Tests, Research and Analysis Methods, Microbiology, General Biochemistry, Genetics and Molecular Biology, Mycobacterium tuberculosis, 03 medical and health sciences, Diagnostic Medicine, In vivo, Microbial Control, Fluorescence Imaging, medicine, Animals, Tuberculosis, Pharmacology, Blood Cells, Bacteria, General Immunology and Microbiology, Macrophages, Organisms, Biology and Life Sciences, Cell Biology, biology.organism_classification, Molecular biology, Computed Axial Tomography, Microscopy, Electron, 030104 developmental biology, chemistry, Bedaquiline, Neuroscience

الوصف: Correlative light, electron, and ion microscopy (CLEIM) offers huge potential to track the intracellular fate of antibiotics, with organelle-level resolution. However, a correlative approach that enables subcellular antibiotic visualisation in pathogen-infected tissue is lacking. Here, we developed correlative light, electron, and ion microscopy in tissue (CLEIMiT) and used it to identify the cell type–specific accumulation of an antibiotic in lung lesions of mice infected with Mycobacterium tuberculosis. Using CLEIMiT, we found that the anti-tuberculosis (TB) drug bedaquiline (BDQ) is localised not only in foamy macrophages in the lungs during infection but also accumulate in polymorphonuclear (PMN) cells.
This study uses correlative light, electron and ion microscopy (CLEIM) in vivo to reveal the intracellular fate of an antibiotic in lung lesions of mice infected with Mycobacterium tuberculosis, with organelle-level resolution.

وصف الملف: application/application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e86f1cbf7c4458b0fe62b3fa72675d57Test
https://doi.org/10.1371/journal.pbio.3000879Test

المؤلفون: Annika Warnatsch, Theodora Dorita Tsourouktsoglou, Maximiliano G. Gutierrez, Susanna Reincke, Nora Branzk, Susanne Herbst, Qian Wang, Venizelos Papayannopoulos

المصدر: Warnatsch, A, Tsourouktsoglou, T D, Branzk, N, Wang, Q, Reincke, S, Herbst, S, Gutierrez, M & Papayannopoulos, V 2017, ' Reactive Oxygen Species Localization Programs Inflammation to Clear Microbes of Different Size ', Immunity, vol. 46, no. 3, pp. 421-432 . https://doi.org/10.1016/j.immuni.2017.02.013Test
Immunity

مصطلحات موضوعية: 0301 basic medicine, Male, Phagocyte, cellular stoichiometry, Neutrophils, interleukin-1β, Immunology, Inflammation, Biology, Article, Microbiology, 03 medical and health sciences, Mice, Immune system, Candida albicans, medicine, Immunology and Allergy, Animals, Humans, cluster, Pathogen, chemistry.chemical_classification, reactive oxygen species, Reactive oxygen species, Bacteria, fungal infection, Interleukin, neutrophil, Bacterial Infections, biology.organism_classification, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, chemistry, Mycoses, Neutrophil Infiltration, inflammation, swarm, Female, microbe size, Mitosporic Fungi, medicine.symptom, Signal transduction, Reactive Oxygen Species

الوصف: Summary How the number of immune cells recruited to sites of infection is determined and adjusted to differences in the cellular stoichiometry between host and pathogen is unknown. Here, we have uncovered a role for reactive oxygen species (ROS) as sensors of microbe size. By sensing the differential localization of ROS generated in response to microbes of different size, neutrophils tuned their interleukin (IL)-1β expression via the selective oxidation of NF-κB, in order to implement distinct inflammatory programs. Small microbes triggered ROS intracellularly, suppressing IL-1β expression to limit neutrophil recruitment as each phagocyte eliminated numerous pathogens. In contrast, large microbes triggered ROS extracellularly, amplifying IL-1β expression to recruit numerous neutrophils forming cooperative clusters. Defects in ROS-mediated microbe size sensing resulted in large neutrophil infiltrates and clusters in response to small microbes that contribute to inflammatory disease. These findings highlight the impact of ROS localization on signal transduction.
Graphical Abstract
Highlights • The clearance of microbes of different size involves distinct inflammatory programs • ROS adjusts neutrophil recruitment to the stoichiometry of host-pathogen interactions • ROS localization acts as a sensor of microbe size to tune IL-1-β-driven inflammation • IL-1β amplifies neutrophil recruitment and clustering to clear large microbes
Inflammation recruits neutrophils to fight invading pathogens of different size. Warnatsch et al. show that reactive oxygen species localization tunes inflammation to compensate for differences in the number of neutrophils required to clear microbes of different size.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa750b25608a6ca29d726d58b3cd5c3fTest
https://kclpure.kcl.ac.uk/ws/files/141617260/Reactive_Oxygen_Species_Localization_Programs_Inflammation_WARNATSCH_Publishedonline14March2017_GOLD_VoR_CC_BY_.pdfTest

المؤلفون: Maximiliano G. Gutierrez, María Verónica Bianco, Thomas R. Lerner, Fabiana Bigi, Cristina Lourdes Vázquez, Achim Gronow, Wolf-Rainer Abraham, Christopher K. E. Bleck, Robert Geffers, Federico Carlos Blanco, Bahram Kasmapour, Gang Pei

المصدر: Cellular Microbiology
Cellular microbiology 16 (9) : 1425-1440. (September 2014)
INTA Digital (INTA)
Instituto Nacional de Tecnología Agropecuaria
instacron:INTA

مصطلحات موضوعية: Intracellular Fluid, Survival, Immunology, Microbiology, Mycobacterium Bovis, Mycobacterium, Mice, Glycolipid, Glicolípidos, Virology, Animals, Gene, 2. Zero hunger, Mice, Inbred BALB C, Mycobacterium Infections, Mycobacterium bovis, Supervivencia, biology, Macrophages, Intracellular parasite, Original Articles, biology.organism_classification, 3. Good health, Long Term Experiments, Líquido Intracellular, Female, Glycolipids, Experimentos de Largo Plazo, Bacteria, Intracellular

الوصف: Some intracellular bacteria are known to cause long‐term infections that last decades without compromising the viability of the host. Although of critical importance, the adaptations that intracellular bacteria undergo during this long process of residence in a host cell environment remain obscure. Here, we report a novel experimental approach to study the adaptations of mycobacteria imposed by a long‐term intracellular lifestyle. Selected Mycobacterium bovis BCG through continuous culture in macrophages underwent an adaptation process leading to impaired phenolic glycolipids (PGL) synthesis, improved usage of glucose as a carbon source and accumulation of neutral lipids. These changes correlated with increased survival of mycobacteria in macrophages and mice during re‐infection and also with the specific expression of stress‐ and survival‐related genes. Our findings identify bacterial traits implicated in the establishment of long‐term cellular infections and represent a tool for understanding the physiological states and the environment that bacteria face living in fluctuating intracellular environments. Instituto de Biotecnología Fil: Vazquez, Cristina Lourdes. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Helmholtz Centre for Infection Research. Research Group Phagosome Biology; Alemania Fil: Lerner, Thomas R. National Institute for Medical Research. Medical Research Council. Division of Mycobacterial Research; Gran Bretaña Fil: Kasmapour, Bahram. Helmholtz Centre for Infection Research. Research Group Phagosome Biology; Alemania Fil: Pei, Gang. Helmholtz Centre for Infection Research. Research Group Phagosome Biology; Alemania Fil: Gronow, Achim. Helmholtz Centre for Infection Research. Research Group Phagosome Biology; Alemania Fil: Bianco, María Veronica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Bleck, Christopher K.E. University of Basel. Centre for Cellular Imaging and NanoAnalytics, Structural Biology and Biophysics, Biozentrum, Mattenstrasse 26; Suiza Fil: Geffers, Robert. Helmholtz Centre for Infection Research. Research Group Genome Analytics; Alemania Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Abraham, Wolf-Rainer. Helmholtz Centre for Infection Research. Research Group Chemical Microbiology; Alemania Fil: Gutierrez, Maximiliano Gabriel. Helmholtz Centre for Infection Research. Research Group Phagosome Biology; Alemania. National Institute for Medical Research. Medical Research Council. Division of Mycobacterial Research; Gran Bretaña

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99fdb90f6d478e550fe6970ab861b1e2Test
https://doi.org/10.1111/cmi.12303Test

المؤلفون: Urska Repnik, Maximiliano G. Gutierrez, Robert J. Wilkinson, Laura Schnettger, Angela Rodgers, Martijn Verdoes, Gang Pei, Douglas Young, Rachel P. J. Lai

المساهمون: Wellcome Trust

المصدر: Cell Host & Microbe
Cell Host & Microbe, 21, 5, pp. 619-628 e5
Cell Host & Microbe, 21, 619-628 e5
628.e5

مصطلحات موضوعية: 0301 basic medicine, Cell Culture Techniques, mycobacterium, Mice, 1108 Medical Microbiology, Phagosomes, INFECTION, Macrophage, IN-VIVO, Phagosome, Rab GTPases, respiratory system, phagosome, 3. Good health, Cell biology, Protein Transport, tuberculosis, Host-Pathogen Interactions, AUTOPHAGY, Female, MYCOBACTERIUM-TUBERCULOSIS, Life Sciences & Biomedicine, 0605 Microbiology, Tuberculosis, 030106 microbiology, Immunology, chemical and pharmacologic phenomena, INNATE, macrophage, Endosomes, Biology, Microbiology, DENDRITIC CELLS, MATURATION, Mycobacterium tuberculosis, 03 medical and health sciences, Interferon-gamma, Short Article, Spatio-Temporal Analysis, Downregulation and upregulation, Bacterial Proteins, Virology, Organelle, medicine, Rab20, Animals, Humans, Antigens, Bacterial, Science & Technology, Membranes, Sequence Analysis, RNA, Macrophages, Sputum, DEGRADATION, medicine.disease, biology.organism_classification, bacterial infections and mycoses, Mice, Inbred C57BL, Cytosol, Disease Models, Animal, 030104 developmental biology, RAW 264.7 Cells, rab GTP-Binding Proteins, VIRULENCE, Parasitology, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Mycobacterium

الوصف: Summary The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within phagosomes and also disrupts these organelles to access the cytosol. The host pathways and mechanisms that contribute to maintaining Mtb phagosome integrity have not been investigated. Here, we examined the spatiotemporal dynamics of Mtb-containing phagosomes and identified an interferon-gamma-stimulated and Rab20-dependent membrane trafficking pathway in macrophages that maintains Mtb in spacious proteolytic phagolysosomes. This pathway functions to promote endosomal membrane influx in infected macrophages, and is required to preserve Mtb phagosome integrity and control Mtb replication. Rab20 is specifically and significantly upregulated in the sputum of human patients with active tuberculosis. Altogether, we uncover an immune-regulated cellular pathway of defense that promotes maintenance of Mtb within intact membrane-bound compartments for efficient elimination.
Graphical Abstract
Highlights • The spatiotemporal dynamics of the M. tuberculosis (Mtb) phagosome were investigated • A Rab20-dependent pathway regulates endocytic influx into Mtb phagosomes • Mtb avoids targeting to Rab20-positive phagosomes through its ESX-1 system • Rab20 is required to maintain Mtb phagosome integrity and for control of Mtb replication
Host-dependent mechanisms that regulate the M. tuberculosis (Mtb) phagosome are unexplored. Schnettger et al. investigate the spatiotemporal dynamics of Mtb phagosomes and identify an IFN-γ-stimulated, Rab20-dependent membrane trafficking pathway in macrophages that maintains Mtb in spacious proteolytic phagolysosomes and is required for mycobacterial control.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2d5cccdccc4ce15d398c3fcf085392e1Test
http://europepmc.org/articles/PMC5432432Test

المؤلفون: Eric J. Thomas, Barry N Kreiswith, Steven Park, Ajanta Chakraborty, Lydia Tabernero, Charis R Saville, Jennifer S. Cavet, Natalia Kurepina, Ana P G Silva, Clare F. Vickers, Maximiliano G. Gutierrez, Paulina Fernandez, David S. Perlin, Laura Schnettger, Yandi Naranjo, Miquel Pons

المساهمون: Universitat de Barcelona

المصدر: Recercat. Dipósit de la Recerca de Catalunya
instname
Dipòsit Digital de la UB
Universidad de Barcelona

مصطلحات موضوعية: Male, Models, Molecular, 0301 basic medicine, Tuberculosis, Protein Conformation, medicine.drug_class, Tuberculosi, Guinea Pigs, Antibiotics, Antitubercular Agents, 01 natural sciences, Virulence factor, Microbiology, Mycobacterium tuberculosis, Structure-Activity Relationship, 03 medical and health sciences, Fosforilació, Bacterial Proteins, In vivo, Tuberculosis, Multidrug-Resistant, Drug Discovery, medicine, Animals, Multidrug-Resistant Mycobacterium tuberculosis, Phosphorylation, Molecular Structure, biology, 010405 organic chemistry, Chemistry, Macrophages, Antimicrobial, medicine.disease, biology.organism_classification, Drug Resistance, Multiple, 0104 chemical sciences, 3. Good health, 030104 developmental biology, Drug Design, Molecular Medicine, Structure based, Female, Protein Tyrosine Phosphatases

الوصف: [Image: see text] Mycobacterium tuberculosis protein-tyrosine-phosphatase B (MptpB) is a secreted virulence factor that subverts antimicrobial activity in the host. We report here the structure-based design of selective MptpB inhibitors that reduce survival of multidrug-resistant tuberculosis strains in macrophages and enhance killing efficacy by first-line antibiotics. Monotherapy with an orally bioavailable MptpB inhibitor reduces infection burden in acute and chronic guinea pig models and improves the overall pathology. Our findings provide a new paradigm for tuberculosis treatment.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fab372acc4fc0cd48b1bbd78ce3550b7Test
http://hdl.handle.net/2445/138558Test