Imperial College London

DrSergeMostowy

Faculty of MedicineDepartment of Medicine

Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 3072s.mostowy

 
 
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Location

 

2.42Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

70 results found

Liew N, Mazon Maya M, Wierzbicki C, Hollinshead M, Dillon M, Thornton C, Ellison A, Cable J, Fisher M, Mostowy Set 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.

JOURNAL ARTICLE

Mostowy S, Chytrid fungus infection in zebrafish demonstrates that the pathogen can parasitise non-amphibian vertebrate hosts, Nature Communications

JOURNAL ARTICLE

McCarthy RR, Mazon-Moya MJ, Moscoso JA, Hao Y, Lam JS, Bordi C, Mostowy S, Filloux Aet 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.

JOURNAL ARTICLE

Mesquita FS, Brito C, Mazon Moya MJ, Pinheiro JC, Mostowy S, Cabanes D, Sousa Set 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

JOURNAL ARTICLE

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Arozena AA, Adachi H, Adams CM, Adams PD, Adeli K, Adhihetty PJ, Adler SG, Agam G, Agarwal R, Aghi MK, Agnello M, Agostinis P, Aguilar PV, Aguirre-Ghiso J, Airoldi EM, Ait-Si-Ali S, Akematsu T, Akporiaye ET, Al-Rubeai M, Albaiceta GM, Albanese C, Albani D, Albert ML, Aldudo J, Alguel H, Alirezaei M, Alloza I, Almasan A, Almonte-Beceril M, Alnemri ES, Alonso C, Altan-Bonnet N, Altieri DC, Alvarez S, Alvarez-Erviti L, Alves S, Amadoro G, Amano A, Amantini C, Ambrosio S, Amelio I, Amer AO, Amessou M, Amon A, An Z, Anania FA, Andersen SU, Andley UP, Andreadi CK, Andrieu-Abadie N, Anel A, Ann DK, Anoopkumar-Dukie S, Antonioli M, Aoki H, Apostolova N, Aquila S, Aquilano K, Araki K, Arama E, Aranda A, Araya J, Arcaro A, Arias E, Arimoto H, Ariosa AR, Armstrong JL, Arnould T, Arsov I, Asanuma K, Askanas V, Asselin E, Atarashi R, Atherton SS, Atkin JD, Attardi LD, Auberger P, Auburger G, Aurelian L, Autelli R, Avagliano L, Avantaggiati ML, Avrahami L, Awale S, Azad N, Bachetti T, Backer JM, Bae D-H, Bae J-S, Bae O-N, Bae SH, Baehrecke EH, Baek S-H, Baghdiguian S, Bagniewska-Zadworna A, Bai H, Bai J, Bai X-Y, Bailly Y, Balaji KN, Balduini W, Ballabio A, Balzan R, Banerjee R, Banhegyi G, Bao H, Barbeau B, Barrachina MD, Barreiro E, Bartel B, Bartolome A, Bassham DC, Bassi MT, Bast RC, Basu A, Batista MT, Batoko H, Battino M, Bauckman K, Baumgarner BL, Bayer KU, Beale R, Beaulieu J-F, Beck GR, Becker C, Beckham JD, Bedard P-A, Bednarski PJ, Begley TJ, Behl C, Behrends C, Behrens GMN, Behrns KE, Bejarano E, Belaid A, Belleudi F, Benard G, Berchem G, Bergamaschi D, Bergami M, Berkhout B, Berliocchi L, Bernard A, Bernard M, Bernassola F, Bertolotti A, Bess AS, Besteiro S, Bettuzzi S, Bhalla S, Bhattacharyya S, Bhutia SK, Biagosch C, Bianchi MW, Biard-Piechaczyk M, Billes V, Bincoletto C, Bingol B, Bird SW, Bitoun M, Bjedov I, Blackstone C, Blanc L, Blanco GA, Blomhoff HK, Boada-Romero E, Boeckler S, Boes M, Boesze-Battaglet al., 2016, Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition), AUTOPHAGY, Vol: 12, Pages: 1-222, ISSN: 1554-8627

JOURNAL ARTICLE

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.

JOURNAL ARTICLE

Krokowski S, Mostowy S, 2016, Interactions between Shigella flexneri and the Autophagy Machinery, FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, Vol: 6, ISSN: 2235-2988

JOURNAL ARTICLE

Krokowski S, Mostowy S, 2016, Investigation of septins using infection by bacterial pathogens, SEPTINS, Vol: 136, Pages: 117-134, ISSN: 0091-679X

JOURNAL ARTICLE

Larrouy-Maumus G, Clements A, Filloux A, McCarthy RR, Mostowy Set 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

JOURNAL ARTICLE

Lobato-Marquez D, Mostowy S, 2016, Septins recognize micron-scale membrane curvature, JOURNAL OF CELL BIOLOGY, Vol: 213, Pages: 5-6, ISSN: 0021-9525

JOURNAL ARTICLE

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

CONFERENCE PAPER

Shah A, Kannambath S, Herbst S, Rogers A, Soresi S, Carby M, Reed A, Mostowy S, Fisher MC, Shaunak S, Armstrong-James DPet 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

JOURNAL ARTICLE

Sirianni A, Krokowski S, Lobato-Marquez D, Buranyi S, Pfanzelter J, Galea D, Willis A, Culley S, Henriques R, Larrouy-Maumus G, Hollinshead M, Sancho-Shimizu V, Way M, Mostowy Set al., 2016, Mitochondria mediate septin cage assembly to promote autophagy of Shigella, EMBO REPORTS, Vol: 17, Pages: 1029-1043, ISSN: 1469-221X

JOURNAL ARTICLE

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.

JOURNAL ARTICLE

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

JOURNAL ARTICLE

Willis AR, Moore C, Mazon-Moya M, Krokowski S, Lambert C, Till R, Mostowy S, Sockett REet 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

JOURNAL ARTICLE

Gibbings D, Mostowy S, Jay F, Schwab Y, Cossart P, Voinnet Oet al., 2015, Corrigendum: Selective autophagy degrades DICER and AGO2 and regulates miRNA activity., Nat Cell Biol, Vol: 17

JOURNAL ARTICLE

Herbst S, Shah A, Moya MM, Marzola V, Jensen B, Reed A, Birrell MA, Saijo S, Mostowy S, Shaunak S, Armstrong-James Det 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

JOURNAL ARTICLE

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

JOURNAL ARTICLE

Shah A, Kannambath S, Herbst S, Rogers A, Carby M, Reed A, Mostowy S, Shaunak S, Armstrong-James Det 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

CONFERENCE PAPER

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.

BOOK CHAPTER

Mostowy S, 2014, Multiple Roles of the Cytoskeleton in Bacterial Autophagy, PLOS PATHOGENS, Vol: 10, ISSN: 1553-7366

JOURNAL ARTICLE

Mostowy S, Bi E, Fuchtbauer E-M, Goryachev AB, Montagna C, Nagata K-I, Trimble WS, Werner HB, Yao X, Zieger B, Spiliotis ETet al., 2014, Highlight: The 5th International Workshop on Septin Biology, BIOLOGICAL CHEMISTRY, Vol: 395, Pages: 119-121, ISSN: 1431-6730

JOURNAL ARTICLE

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

JOURNAL ARTICLE

Ghossoub R, Hu Q, Failler M, Rouyez MC, Spitzbarth B, Mostowy S, Wolfrum U, Saunier S, Cossart P, Jamesnelson W, Benmerah Aet 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.

JOURNAL ARTICLE

Gibbings D, Mostowy S, Voinnet O, 2013, Autophagy selectively regulates miRNA homeostasis, AUTOPHAGY, Vol: 9, Pages: 781-783, ISSN: 1554-8627

JOURNAL ARTICLE

Guenin-Macé L, Veyron-Churlet R, Thoulouze MI, Romet-Lemonne G, Hong H, Leadlay PF, Danckaert A, Ruf MT, Mostowy S, Zurzolo C, Bousso P, Chrétien F, Carlier MF, Demangel Cet 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.

JOURNAL ARTICLE

Judith D, Mostowy S, Bourai M, Gangneux N, Lelek M, Lucas-Hourani M, Cayet N, Jacob Y, Prévost MC, Pierre P, Tangy F, Zimmer C, Vidalain PO, Couderc T, Lecuit Met 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.

JOURNAL ARTICLE

Mostowy S, 2013, Autophagy and bacterial clearance: a not so clear picture, CELLULAR MICROBIOLOGY, Vol: 15, Pages: 395-402, ISSN: 1462-5814

JOURNAL ARTICLE

Mostowy S, Boucontet L, Moya MJM, Sirianni A, Boudinot P, Hollinshead M, Cossart P, Herbomel P, Levraud J-P, Colucci-Guyon Eet 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

JOURNAL ARTICLE

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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