{"id":38631,"date":"2019-08-05T12:56:43","date_gmt":"2019-08-05T10:56:43","guid":{"rendered":"https:\/\/aktuelles.uni-frankfurt.de\/?p=38631"},"modified":"2023-02-22T17:35:56","modified_gmt":"2023-02-22T16:35:56","slug":"surprising-insight-into-legionnaires-disease","status":"publish","type":"post","link":"https:\/\/aktuelles.uni-frankfurt.de\/en\/english\/surprising-insight-into-legionnaires-disease\/","title":{"rendered":"Surprising insight into Legionnaires\u2019 disease"},"content":{"rendered":"\n<div class=\"wp-block-image\"><figure class=\"aligncenter\"><img fetchpriority=\"high\" decoding=\"async\" width=\"650\" height=\"450\" src=\"https:\/\/aktuelles.uni-frankfurt.de\/wp-content\/uploads\/2019\/07\/blog_Legionellen.jpg\" alt=\"\" class=\"wp-image-38571\" srcset=\"https:\/\/aktuelles.uni-frankfurt.de\/wp-content\/uploads\/2019\/07\/blog_Legionellen.jpg 650w, https:\/\/aktuelles.uni-frankfurt.de\/wp-content\/uploads\/2019\/07\/blog_Legionellen-300x208.jpg 300w\" sizes=\"(max-width: 650px) 100vw, 650px\" \/><\/figure><\/div>\n\n\n\n<p><strong><em>Frankfurt researchers have explained the mechanism of regulator SidJ in detail \/ Accelerated publication in Nature<\/em><\/strong><\/p>\n\n\n\n<p>In order to control cellular processes and thwart the immune system, the bacterium <em>Legionella pneumophilia<\/em>, the cause of the notorious Legionnaires\u2019 disease, releases hundreds of enzymes. Biochemists at Goethe University have now elucidated important details in the interaction of bacterial effectors. They discovered how the regulatory enzyme SidJ keeps other dangerous virulence factors in check.<\/p>\n\n\n\n<p>The incidence of Legionnaires\u2019 disease has increased in\nthe past two decades. The natural habitat of <em>Legionella<\/em> is freshwater biotopes, where they mainly reproduce in\namoebae. In addition, <em>Legionella<\/em> can\nalso colonize water tanks or pipes and spread, for example, via poorly\nmaintained air-conditioning systems. Contaminated aerosols are released into the air\nand trigger the infection. The pathogens cause, among others, pneumonia, which is\noften fatal in elderly patients or individuals with a weak immune system. <\/p>\n\n\n\n<p>What makes <em>Legionella<\/em>\nso dangerous is its ability to multiply in phagocytes of the immune system by\nsecreting virulence factors. Some of these effectors \u2013 the enzymes of what is\nknown as the SidE family \u2013 are so toxic that without tight control they would\ninstantly kill their host cells. However, since <em>Legionella<\/em> needs the host cells in order to multiply, it has\ndeveloped a sophisticated mechanism for the precise metering of SidE enzyme\nactivity. Details of this process are now reported by scientists at Goethe\nUniversity and from Grenoble in the journal <em>Nature<\/em>.<\/p>\n\n\n\n<p>They have shown that the regulator SidJ also released\nby <em>Legionella<\/em> works as an antidote to\nSidE enzymes, thus ensuring accurate control of SidE activity. The SidJ\nregulator is a glutamylase, i.e. it has a rare enzyme activity that allows\namino acid glutamates to be linked together to form chains. In this case, SidJ\nattacks the central glutamate of SidE enzymes and inhibits their activity. So\nfar, little is known about glutamylases \u2013 so the scientists were all the more\nsurprised when they discovered that it is precisely this type of enzyme which\nis important for the coordinated interaction of the virulence factors of <em>Legionella<\/em>.<\/p>\n\n\n\n<p>\u201cThis is a typical example of how completely\nunpredictable results drive research. Such discoveries are what make science\nsuch a fascinating and exciting profession,\u201d says Professor Ivan Dikic from the\nInstitute of Biochemistry II and the Buchmann Institute for Molecular Life\nSciences at Goethe University. \u201cWe can only gain a molecular understanding of\nthe complex world of bacterial infections by working in interdisciplinary teams\nand combining methods from modern biochemistry and proteomics with cell and\nstructural biology techniques.\u201d<\/p>\n\n\n\n<p>The researchers also revealed how SidJ is activated in\nhost cells: It requires the calcium-binding protein calmodulin found in\nmammalian cells. Cryo-electron microscopy played an important role in explaining\nthe structure of the calmodulin-SidJ complex. \u201cGlutamylation as a protein\nmodification is understudied. Our finding that <em>Legionella pneumophilia<\/em> uses exactly this mechanism to sustain the\ninfection certainly argues for more research in this field. For example, the\nextent to which <em>Legionella<\/em> utilizes\nthis modification to regulate other cellular processes is completely unclear,\u201d\nexplains Dr. Sagar Bhogaraju, who led the microscopic examinations at the\nEuropean Molecular Biology Laboratory (EMBL) in Grenoble.<\/p>\n\n\n\n<p>This so far unknown mechanism opens up new\npossibilities for research to inhibit the spread of <em>Legionella<\/em> in the host organism. \u201cWe\u2019re currently working on eliminating\nSidJ selectively by developing inhibitors for the glutamylase domain. In\naddition to the use of antibiotics, they could prevent the spread of <em>Legionella pneumophilia <\/em>in phagocytes,\u201d\nexplains Dikic.<\/p>\n\n\n\n<p class=\"has-background has-very-light-gray-background-color\"><strong>Publication<\/strong>: <br>Sagar Bhogaraju, Florian Bonn, Rukmini Mukherjee, Michael Adams, Moritz M. Pfleiderer, Wojciech P. Galej, Vigor Matkovic, Sissy Kalayil, Donghyuk <a>Shin<\/a><a href=\"#_msocom_1\">[S1]<\/a>\u00a0, Ivan Dikic: Inhibition of SidE ubiquitin ligases through SidJ\/Calmodulin catalyzed glutamylation, in Nature 22. Juli 2019 DOI: 10.1038\/s41586-019-1440-8  <a href=\"https:\/\/www.nature.com\/articles\/s41586-019-1440-8\">https:\/\/www.nature.com\/articles\/s41586-019-1440-8<\/a> <\/p>\n\n\n\n<p><strong><em>Source: Press release from 24 July 2019<\/em><\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Frankfurt researchers have explained the mechanism of regulator SidJ in detail \/ Accelerated publication in Nature In order to control cellular processes and thwart the immune system, the bacterium Legionella [&hellip;]<\/p>\n","protected":false},"author":8,"featured_media":38571,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_eb_attr":"","_price":"","_stock":"","_tribe_ticket_header":"","_tribe_default_ticket_provider":"","_ticket_start_date":"","_ticket_end_date":"","_tribe_ticket_show_description":"","_tribe_ticket_show_not_going":false,"_tribe_ticket_use_global_stock":"","_tribe_ticket_global_stock_level":"","_global_stock_mode":"","_global_stock_cap":"","_tribe_rsvp_for_event":"","_tribe_ticket_going_count":"","_tribe_ticket_not_going_count":"","_tribe_tickets_list":"[]","_tribe_ticket_has_attendee_info_fields":false,"footnotes":""},"categories":[126,254],"tags":[243],"post_folder":[],"class_list":["post-38631","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-english","category-research","tag-biochemistry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - 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