{"id":12444,"date":"2019-11-22T10:27:51","date_gmt":"2019-11-22T17:27:51","guid":{"rendered":"http:\/\/canadianglycomics.ca\/?p=12444"},"modified":"2019-11-22T10:27:52","modified_gmt":"2019-11-22T17:27:52","slug":"the-secret-life-of-bacterial-phosphonate-biosynthesis-revealed","status":"publish","type":"post","link":"https:\/\/canadianglycomics.ca\/fr\/the-secret-life-of-bacterial-phosphonate-biosynthesis-revealed\/","title":{"rendered":"The secret life of bacterial phosphonate biosynthesis, revealed"},"content":{"rendered":"

GlycoNet scientists identified an enzyme possibly related to bacterial virulence and antibiotic resistance<\/p>\n\n\n\n

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GlycoNet scientists team revealed an enzyme that is possible related to bacteria infection and resistance mechanisms. From left: Geoff Horsman, Michael Suits, Joel Weadge.<\/figcaption><\/figure>\n\n\n\n

By Ali Chou<\/p>\n\n\n\n

For\ndecades, antibiotics have been the mainstay to combat bacterial infections.\nUnfortunately, with the overuse and misuse of antibiotics, resistant bacteria\nare emerging and spreading globally, threatening our ability to treat common\ninfectious diseases. In addition, using broad-spectrum antibiotics when the\ncausative agent of an infection is unknown can result in unintended\nconsequences, as these antibiotics can kill the \u2018good\u2019 bacteria in our body. It\nis crucial to gain deeper understanding of the infection and resistance\nmechanisms in bacteria in order to find new methods to tackle drug resistance,\nas well as developing more targeted treatments. <\/p>\n\n\n\n

In\na recent study published in Nature Communications<\/a>, GlycoNet scientists Geoff\nHorsman, Joel Weadge, and Michael Suits, together with researchers Marc Van der\nKamp from the University of Bristol and Gabriel Moreno-Hagelsieb from Wilfrid\nLaurier University, have made a significant stride in identifying key elements\nthat may help bacteria invade and survive in the host. The team discovered an enzyme,\na nucleotidyltransferase, that initiates the biosynthesis of bacterial\nphosphonates\u2014a complex process where small molecule phosphonates are attached\nto glycans in the bacteria and presented onto bacterial cell surface. This\nprocess may hold clues to how bacteria evade detection from the host immune\nsystem.<\/p>\n\n\n\n

In\nbacteria, small molecule phosphonates are often observed at the cell surface where\nthey are attached to glycans. However, little is known about the biological\nroles of these phosphonylated glycans or the steps involved in assembling them.\nWhat\u2019s more puzzling is that it seems small molecule phosphonates originate\nfrom the inside of the cell\u2014how do they end up on the bacterial cell surface?<\/p>\n\n\n\n

To\nanswer the question, Horsman and his team first looked at over 100,000 genomes\nfrom different bacteria and located clusters of genes predicted to assemble phosphonylated\nglycans. In bacteria, a cluster of genes consists of several genes that encode proteins\nwith similar functions. In this case, proteins that are involved in making\nphosphonylated glycans, or phosphonate biosynthesis, would locate in a cluster.<\/p>\n\n\n\n

The\nteam soon discovered something unexpected. Over two-thirds of the clusters\ncontain the same genes encoding nucleotidyltransferases. \u201cWe were surprised by\nthe unusually large proportion of gene clusters possessing\nnucleotidyltransferases,\u201d says Horsman. \u201cThis was not previously reported or\neven suspected.\u201d The discovery strongly suggests that nucleotidyltransferases\nhave been widely recruited for phosphonate biosynthesis, but the evolutionary pressure\nunderlying this recruitment remains unclear. <\/p>\n\n\n\n

To\ngain a better understanding of the functional role and biological properties of\nthese nucleotidyltransferases, the researchers used a combination of methods\nincluding crystallography, molecular dynamics simulations, mass spectrometry,\nliquid chromatography, and nuclear magnetic resonance spectroscopy. Like\npiecing together a puzzle, the team gathered bits of information from each\nmethod and deduced a mechanism of the enzyme. <\/p>\n\n\n\n

\u201cWe\nthink these nucleotidyltransferases initiate the biosynthesis by activating\nsmall molecule phosphonates inside the cell,\u201d says Horsman. By \u2018activation,\u2019 it\nmeans to modify the structure of phosphonates chemically so that they are ready\nfor subsequent steps in the biosynthesis. The activated phosphonates are then\npresumably captured by glycans or lipids that are anchored at the cell\nmembrane. <\/p>\n\n\n\n

Steps\nbeyond the activation of phosphonates are still unclear, but Horsman says that\nfurther studies will attempt to tease out other key players involved in the\nbiosynthetic pathway to understand how phosphonates end up on bacterial cell\nsurfaces.<\/p>\n\n\n\n

Although\nthere are still many mysteries about bacterial metabolic pathways, the team\u2019s\nwork on nucleotidyltransferases and their involvement in phosphonate\nbiosynthesis sets the stage for many opportunities and potential applications. Horsman\npoints out that it is highly possible that the biosynthesis of phosphonates is\nassociated with bacterial survival in the host. \u201cBased on analogies to other\nbacterial systems, where modification of cell surface molecules is a mechanism\nof bacterial virulence, we think that phosphonylated glycans could similarly be\nrelated to host cell invasion or hiding from the immune system,\u201d he says. This\nmeans that nucleotidyltransferases could potentially be a novel target for\ndeveloping targeted antivirulence agents to battle drug resistance in bacteria.\nThe team plans to conduct more studies to investigate the impact of these\nenzymes in bacterial survival and pathogen-host interactions.<\/p>\n\n\n\n

This research was supported by GlycoNet, NSERC, Wilfrid Laurier University and the Royal Society of Chemistry. <\/p>","protected":false},"excerpt":{"rendered":"

GlycoNet scientists identified an enzyme possibly related to bacterial virulence and antibiotic resistance.<\/p>","protected":false},"author":2,"featured_media":12445,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"om_disable_all_campaigns":false,"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[203],"tags":[],"class_list":["post-12444","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research-highlight","wpbf-post"],"aioseo_notices":[],"aioseo_head":"\n\t\t\n\t\n\t\n\t\n\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t