70 results found
Liew N, Mazon Maya M, Wierzbicki C, et al., Chytrid fungus infection in zebrafish demonstrates that the pathogen can parasitise non-amphibian vertebrate hosts, Nature Communications, ISSN: 2041-1723
Aquatic chytrid fungi threaten amphibian biodiversity worldwide owing to their ability torapidly expand their geographical distributions and to infect a wide range of hosts. Combatingthis risk requires an understanding of chytrid host range to identify potential reservoirsof infection and to safeguard uninfected regions through enhanced biosecurity. Here weextend our knowledge on the host range of the chytridBatrachochytrium dendrobatidisby demonstrating infection of a non-amphibian vertebrate host, the zebrafish. We observedose-dependent mortality and show that chytrid can infect and proliferate on zebrafish tissue.We also show that infection phenotypes (fin erosion, cell apoptosis and muscle degeneration)are direct symptoms of infection. Successful infection is dependent on disrupting thezebrafish microbiome, highlighting that, as is widely found in amphibians, commensalbacteria confer protection against this pathogen. Collectively, our findings greatly expand thelimited tool kit available to study pathogenesis and host response to chytrid infection.
Mostowy S, Chytrid fungus infection in zebrafish demonstrates that the pathogen can parasitise non-amphibian vertebrate hosts, Nature Communications
McCarthy RR, Mazon-Moya MJ, Moscoso JA, et al., 2017, Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion., Nat Microbiol, Vol: 2
Pseudomonas aeruginosa is a Gram-negative bacterial pathogen associated with acute and chronic infections. The universal cyclic-di-GMP second messenger is instrumental in the switch from a motile lifestyle to resilient biofilm as in the cystic fibrosis lung. The SadC diguanylate cyclase is associated with this patho-adaptive transition. Here, we identify an unrecognized SadC partner, WarA, which we show is a methyltransferase in complex with a putative kinase, WarB. We established that WarA binds to cyclic-di-GMP, which potentiates its methyltransferase activity. Together, WarA and WarB have structural similarities with the bifunctional Escherichia coli lipopolysaccharide (LPS) O antigen regulator WbdD. Strikingly, WarA influences P. aeruginosa O antigen modal distribution and interacts with the LPS biogenesis machinery. LPS is known to modulate the immune response in the host, and by using a zebrafish infection model, we implicate WarA in the ability of P. aeruginosa to evade detection by the host.
Mesquita FS, Brito C, Mazon Moya MJ, et al., 2017, Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins, EMBO REPORTS, Vol: 18, Pages: 303-318, ISSN: 1469-221X
Klionsky DJ, Abdelmohsen K, Abe A, et al., 2016, Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition), AUTOPHAGY, Vol: 12, Pages: 1-222, ISSN: 1554-8627
Krokowski S, Lobato-Márquez D, Mostowy S, 2016, Mitochondria promote septin assembly into cages that entrap Shigella for autophagy., Autophagy
Septins are cytoskeletal proteins implicated in cytokinesis and host-pathogen interactions. During macroautophagy/autophagy of Shigella flexneri, septins assemble into cage-like structures to entrap actin-polymerizing bacteria and restrict their dissemination. How septins assemble to entrap bacteria is not fully known. We discovered that mitochondria support septin cage assembly to promote autophagy of Shigella. Consistent with roles for the cytoskeleton in mitochondrial dynamics, we showed that DNM1L/DRP1 (dynamin 1 like) can interact with septins to enhance mitochondrial fission. Remarkably, Shigella fragment mitochondria and escape from septin cage entrapment in order to avoid autophagy. These results uncover a close relationship between mitochondria and septin assembly, and identify a new role for mitochondria in bacterial autophagy.
Krokowski S, Mostowy S, 2016, Interactions between Shigella flexneri and the Autophagy Machinery, FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, Vol: 6, ISSN: 2235-2988
Krokowski S, Mostowy S, 2016, Investigation of septins using infection by bacterial pathogens, SEPTINS, Vol: 136, Pages: 117-134, ISSN: 0091-679X
Larrouy-Maumus G, Clements A, Filloux A, et al., 2016, Direct detection of lipid A on intact Gram-negative bacteria by MALDI-TOF mass spectrometry, JOURNAL OF MICROBIOLOGICAL METHODS, Vol: 120, Pages: 68-71, ISSN: 0167-7012
Lobato-Marquez D, Mostowy S, 2016, Septins recognize micron-scale membrane curvature, JOURNAL OF CELL BIOLOGY, Vol: 213, Pages: 5-6, ISSN: 0021-9525
Pfanzelter J, Way M, Mostowy S, 2016, Septins suppress the release of vaccinia virus from infected cells., Annual Meeting of the American-Society-for-Cell-Biology (ASCB), Publisher: AMER SOC CELL BIOLOGY, ISSN: 1059-1524
Shah A, Kannambath S, Herbst S, et al., 2016, Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 194, Pages: 1127-1139, ISSN: 1073-449X
Sirianni A, Krokowski S, Lobato-Marquez D, et al., 2016, Mitochondria mediate septin cage assembly to promote autophagy of Shigella, EMBO REPORTS, Vol: 17, Pages: 1029-1043, ISSN: 1469-221X
Torraca V, Mostowy S, 2016, Septins and Bacterial Infection., Front Cell Dev Biol, Vol: 4
Septins, a unique cytoskeletal component associated with cellular membranes, are increasingly recognized as having important roles in host defense against bacterial infection. A role for septins during invasion of Listeria monocytogenes into host cells was first proposed in 2002. Since then, work has shown that septins assemble in response to a wide variety of invasive bacterial pathogens, and septin assemblies can have different roles during the bacterial infection process. Here we review the interplay between septins and bacterial pathogens, highlighting septins as a structural determinant of host defense. We also discuss how investigation of septin assembly in response to bacterial infection can yield insight into basic cellular processes including phagocytosis, autophagy, and mitochondrial dynamics.
Willis A, Mazon-Moya M, Mostowy S, 2016, Investigation of septin biology in vivo using zebrafish, SEPTINS, Vol: 136, Pages: 221-241, ISSN: 0091-679X
Willis AR, Moore C, Mazon-Moya M, et al., 2016, Injections of Predatory Bacteria Work Alongside Host Immune Cells to Treat Shigella Infection in Zebrafish Larvae, CURRENT BIOLOGY, Vol: 26, Pages: 3343-3351, ISSN: 0960-9822
Gibbings D, Mostowy S, Jay F, et al., 2015, Corrigendum: Selective autophagy degrades DICER and AGO2 and regulates miRNA activity., Nat Cell Biol, Vol: 17
Herbst S, Shah A, Moya MM, et al., 2015, Phagocytosis-dependent activation of a TLR9-BTK-calcineurin-NFAT pathway co-ordinates innate immunity to Aspergillus fumigatus, EMBO MOLECULAR MEDICINE, Vol: 7, Pages: 240-258, ISSN: 1757-4676
Mostowy S, Shenoy AR, 2015, The cytoskeleton in cell-autonomous immunity: structural determinants of host defence, NATURE REVIEWS IMMUNOLOGY, Vol: 15, Pages: 559-573, ISSN: 1474-1733
Shah A, Kannambath S, Herbst S, et al., 2015, 'THE KISS OF DEATH' - CALCINEURIN INHIBITORS PREVENT ACTIN-DEPENDENT LATERAL TRANSFER OF ASPERGILLUS FUMIGATUS IN NECROPTOTIC HUMAN MACROPHAGES, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A48-A48, ISSN: 0040-6376
Sirianni A, Mostowy S, 2015, Autophagy in the Infected Cell: Insights from Pathogenic Bacteria, Autophagy, Infection, and the Immune Response, Pages: 143-157, ISBN: 9781118677551
© 2015 by John Wiley & Sons, Inc. All rights reserved.Autophagy is an important defence mechanism to clear intracellular microbes. A wide variety of bacterial pathogens are targeted to autophagy; however, some have evolved mechanisms to avoid or manipulate the autophagy machinery for intracellular survival. An in-depth understanding of autophagy-bacteria interactions will therefore be critical to appreciate fully how the autophagy machinery can function in immunity and microbial clearance in vivo.
Mostowy S, 2014, Multiple Roles of the Cytoskeleton in Bacterial Autophagy, PLOS PATHOGENS, Vol: 10, ISSN: 1553-7366
Mostowy S, Bi E, Fuchtbauer E-M, et al., 2014, Highlight: The 5th International Workshop on Septin Biology, BIOLOGICAL CHEMISTRY, Vol: 395, Pages: 119-121, ISSN: 1431-6730
Moya MJM, Colucci-Guyon E, Mostowy S, 2014, Use of Shigella flexneri to Study Autophagy-Cytoskeleton Interactions, JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, ISSN: 1940-087X
Ghossoub R, Hu Q, Failler M, et al., 2013, Septins 2, 7 and 9 and MAP4 colocalize along the axoneme in the primary cilium and control ciliary length., J Cell Sci, Vol: 126, Pages: 2583-2594
Septins are a large, evolutionarily conserved family of GTPases that form hetero-oligomers and interact with the actin-based cytoskeleton and microtubules. They are involved in scaffolding functions, and form diffusion barriers in budding yeast, the sperm flagellum and the base of primary cilia of kidney epithelial cells. We investigated the role of septins in the primary cilium of retinal pigmented epithelial (RPE) cells, and found that SEPT2 forms a 1:1:1 complex with SEPT7 and SEPT9 and that the three members of this complex colocalize along the length of the axoneme. Similar to observations in kidney epithelial cells, depletion of cilium-localized septins by siRNA-based approaches inhibited ciliogenesis. MAP4, which is a binding partner of SEPT2 and controls the accessibility of septins to microtubules, was also localized to the axoneme where it appeared to negatively regulate ciliary length. Taken together, our data provide new insights into the functions and regulation of septins and MAP4 in the organization of the primary cilium and microtubule-based activities in cells.
Gibbings D, Mostowy S, Voinnet O, 2013, Autophagy selectively regulates miRNA homeostasis, AUTOPHAGY, Vol: 9, Pages: 781-783, ISSN: 1554-8627
Guenin-Macé L, Veyron-Churlet R, Thoulouze MI, et al., 2013, Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli ulcer formation., J Clin Invest, Vol: 123, Pages: 1501-1512
Mycolactone is a diffusible lipid secreted by the human pathogen Mycobacterium ulcerans, which induces the formation of open skin lesions referred to as Buruli ulcers. Here, we show that mycolactone operates by hijacking the Wiskott-Aldrich syndrome protein (WASP) family of actin-nucleating factors. By disrupting WASP autoinhibition, mycolactone leads to uncontrolled activation of ARP2/3-mediated assembly of actin in the cytoplasm. In epithelial cells, mycolactone-induced stimulation of ARP2/3 concentrated in the perinuclear region, resulting in defective cell adhesion and directional migration. In vivo injection of mycolactone into mouse ears consistently altered the junctional organization and stratification of keratinocytes, leading to epidermal thinning, followed by rupture. This degradation process was efficiently suppressed by coadministration of the N-WASP inhibitor wiskostatin. These results elucidate the molecular basis of mycolactone activity and provide a mechanism for Buruli ulcer pathogenesis. Our findings should allow for the rationale design of competitive inhibitors of mycolactone binding to N-WASP, with anti-Buruli ulcer therapeutic potential.
Judith D, Mostowy S, Bourai M, et al., 2013, Species-specific impact of the autophagy machinery on Chikungunya virus infection., EMBO Rep, Vol: 14, Pages: 534-544
Chikungunya virus (CHIKV) is a recently re-emerged arbovirus that triggers autophagy. Here, we show that CHIKV interacts with components of the autophagy machinery during its replication cycle, inducing a cytoprotective effect. The autophagy receptor p62 protects cells from death by binding ubiquitinated capsid and targeting it to autophagolysosomes. By contrast, the human autophagy receptor NDP52--but not its mouse orthologue--interacts with the non-structural protein nsP2, thereby promoting viral replication. These results highlight the distinct roles of p62 and NDP52 in viral infection, and identify NDP52 as a cellular factor that accounts for CHIKV species specificity.
Mostowy S, 2013, Autophagy and bacterial clearance: a not so clear picture, CELLULAR MICROBIOLOGY, Vol: 15, Pages: 395-402, ISSN: 1462-5814
Mostowy S, Boucontet L, Moya MJM, et al., 2013, The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy, PLOS PATHOGENS, Vol: 9, ISSN: 1553-7366
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