{"id":4884,"date":"2014-06-05T09:13:48","date_gmt":"2014-06-05T13:13:48","guid":{"rendered":"https:\/\/web.uri.edu\/inbre\/?page_id=4884"},"modified":"2014-06-05T09:13:48","modified_gmt":"2014-06-05T13:13:48","slug":"espinosa","status":"publish","type":"page","link":"https:\/\/web.uri.edu\/riinbre\/research\/surf-training-award\/espinosa\/","title":{"rendered":"Anaerobic enzymes as drug targets in the treatment of amebiasis"},"content":{"rendered":"<p><strong>Investigator:<\/strong>\u00a0Avelina Espinosa, Roger Williams University<\/p>\n<p><strong>Scientific Theme:<\/strong>\u00a0Molecular Toxicology<\/p>\n<p style=\"text-align: justify\"><strong>Abstract:\u00a0<\/strong>Anaerobic protozoan parasites share physiological and biochemical features (e.g. carbohydrate metabolism\u00a0and cytosolic fermentation enzymes) essential to survive in their hosts. Understanding the evolutionary\u00a0adaptations of glycolytic enzymes to luminal environments -in the context of diverse host conditions for\u00a0anaerobic metabolism- can lead to the development of new drugs and\/or improve treatments for infectious\u00a0diseases. Amebiasis is the third leading parasitic cause of death worldwide. As an anaerobic eukaryote, its\u00a0causative agent, Entamoeba histolytica lacks mitochondria and obtains energy from fermenting glucose, with\u00a0carbon dioxide, acetate, and ethanol as end products. This metabolic pathway provides targets for\u00a0developing anti-infective agents (ADHE alcohol\/aldehyde dehydrogenases). During the past 15 years,\u00a0Espinosa et al. have shown that the bifunctional Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2)\u00a0is a glycolytic enzyme essential for the survival of the trophozoite in the luminal environment of humans;\u00a0thus, an ideal target for the development of anti-amebic agents. Because ADHE enzymes are found in\u00a0bacteria (i.e. group-A-streptococcus, Pasteurella multocida, E. coli, Clostridium perfringens, Clostridium\u00a0difficile), and protozoan parasites such as E. histolytica, and differ phylogenetically from human enzymes,\u00a0ADHE targeting chemotherapeutic agents could effectively treat a broad range of human diseases. This\u00a0proposal aims to a) characterize molecular, biochemical and structural properties of alcohol\/aldehyde\u00a0dehydrogenases (ADHE) to design customized antiamebic agents; b) Test novel pyrazolines as inhibitors of\u00a0trophozoite growth and EhADH2 enzyme activities. Studying the adaptations of anaerobic pathogens to the\u00a0luminal environment can change the classical view of infectious diseases to an evolutionary understanding of\u00a0the ecological association between microbionts. By analyzing the structural properties of model anaerobic\u00a0enzymes essential for the survival of the human pathogen Entamoeba histolytica to the human luminal\u00a0environment we can highlight the importance of an evolutionary perspective in the education of students\u00a0interested in pursuing health related professions.<\/p>\n<p style=\"text-align: justify\"><strong>Human Health Relevance:<\/strong>\u00a0EhADH2 is the ideal target for the development of a novel classes of inhibitors to treat amebiasis, the\u00a0gastrointestinal infection caused by E. histolytic that is estimated to cause 100,000 deaths per year. This\u00a0study will provide hands-on experience to help students develop an understanding of the scientific method,\u00a0the critical thinking and technical skills needed to pursue a career in science or in health related areas.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Investigator:\u00a0Avelina Espinosa, Roger Williams University Scientific Theme:\u00a0Molecular Toxicology Abstract:\u00a0Anaerobic protozoan parasites share physiological and biochemical features (e.g. carbohydrate metabolism\u00a0and cytosolic fermentation enzymes) essential to survive in their hosts. Understanding the evolutionary\u00a0adaptations of glycolytic enzymes to luminal environments -in the context of diverse host conditions for\u00a0anaerobic metabolism- can lead to the development of new drugs and\/or [&hellip;]<\/p>\n","protected":false},"author":1036,"featured_media":0,"parent":10206,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"page-twocol.php","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"class_list":["post-4884","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/4884","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/users\/1036"}],"replies":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/comments?post=4884"}],"version-history":[{"count":0,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/4884\/revisions"}],"up":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/10206"}],"wp:attachment":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/media?parent=4884"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}