{"id":95125,"date":"2014-07-23T08:27:23","date_gmt":"2014-07-23T12:27:23","guid":{"rendered":"https:\/\/today.uconn.edu\/?p=95125"},"modified":"2015-12-11T09:19:10","modified_gmt":"2015-12-11T14:19:10","slug":"possible-breakthrough-in-battle-against-drug-resistant-diseases","status":"publish","type":"post","link":"https:\/\/today.uconn.edu\/2014\/07\/possible-breakthrough-in-battle-against-drug-resistant-diseases\/","title":{"rendered":"Possible Breakthrough in Battle Against Drug-Resistant Diseases"},"content":{"rendered":"
\"Amy<\/a>
Amy Anderson, left, and Dennis Wright, both professors of pharmaceutical science. (Peter Morenus\/UConn Photo)<\/figcaption><\/figure>\n

In the war against drug-resistant diseases and so-called \u201csuperbugs\u201d, the family of bacteria known as CREs are a particularly nasty bunch.<\/p>\n

The bacteria, whose scientific name is carbapenem-resistant Enterobacteriaceae \u2013 include notorious strains of E. coli<\/em> and Klebsiella<\/em> and are a constant health concern in hospitals and nursing homes, where the germs breed in ventilators, catheters, and intravenous lines.<\/p>\n

CREs have been flagged as an \u201curgent threat\u201d by the Centers for Disease Control and Prevention because of their strong resistance to antibiotics and easy transmission between humans. Some CRE bacteria are resistant to all known antibiotics. The mortality rate is high. As many as 50 percent of patients infected with CRE bacteria die because there is no drug to fight them.<\/p>\n

But two UConn scientists may be gaining new ground against the public health threat. Professors Amy Anderson and Dennis Wright, along with their students in the School of Pharmacy, have developed a group of drug compounds that appear to be particularly effective against CREs in early tests. A lead is a preliminary molecule that shows promise and is poised for further development.<\/p>\n

The potent compounds \u2013 part of a group of drugs known as antifolates – were a long time coming for the two, who have been searching for effective treatments for drug-resistant diseases like MRSA, E. coli,<\/em> and Klebsiella pneumoniae<\/em> for more than 10 years. Working with drug-resistant strains is particularly challenging for researchers, as the diseases constantly morph and evolve to fend off attacks to kill them.<\/p>\n

We\u2019ve made compounds that are very hard for these [bacteria]\u00a0 to fend off.–Dennis Wright<\/p><\/blockquote>\n

\u201cIt has been a holy grail to kill these types of CREs,\u201d says Anderson, a professor of medicinal chemistry and interim head of the Department of Pharmaceutical Sciences. \u201cThese (CRE) bacteria have an extra thick, tight membrane meshed with proteins that makes it very hard for drugs to penetrate. We\u2019ve spent years trying.\u201d<\/p>\n

After testing hundreds of different compounds, delicately altering each one\u2019s chemical structure with the hope of finding the magic recipe that would serve as a CRE knockout blow, Anderson and Wright recently started seeing positive results in one particular group.<\/p>\n

\u2018Our goal was to inhibit a certain enzyme in the bacteria so it can\u2019t function and the bacteria can\u2019t survive,\u201d Anderson says. \u201cWhen we finally got a very potent inhibition of the enzyme, that was definitely a eureka moment.\u201d<\/p>\n

The pair recently received a five-year, $2.7 million grant from the National Institutes of Health to further study these compounds and prepare them for clinical trials. Together, Anderson\u2019s and Wright\u2019s labs have received more than $10 million in federal research support since they began working on the project.Wright, a professor of medicinal chemistry, synthesizes the new drugs; Anderson evaluates them and determines the atomic details of how they interact with their intended target .<\/p>\n

\u201cWe want to make compounds that are potent inhibitors of the growth of the bacteria and at the same time are safe, with good drug properties, so down the line they will be effective when used at a clinic,\u201d says Wright.<\/p>\n

At this stage in the research, Anderson and Wright are trying to learn more about the physical and chemical processes that allow their compounds to penetrate the armor-like coating around CREs when so many others have failed. Understanding why their compounds are working may allow them to apply the same biological chemistry to different compounds that could be used to fight other persistent infections. Associate professor of pharmacy practice Jeffrey Aeschlimann from UConn Health is helping with the CRE drug characterizations. University of Montana professor of chemistry Nigel Priestley is assisting with testing in early animal pre-clinical trials.<\/p>\n

\u201cRight now, what makes our compounds attractive is that they seem to have a very low rate of resistance,\u201d says Wright. \u201cWe\u2019ve made compounds that are very hard for these CREs to fend off.\u201d<\/p>\n

Read more about UConn\u2019s CRE research here<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"

Two UConn researchers have developed new compounds that appear to be effective against E. coli, MRSA, and other antibiotic-resistant bacteria.<\/p>\n","protected":false},"author":12,"featured_media":88751,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_crdt_document":"","wds_primary_category":0,"wds_primary_series":0,"wds_primary_attribution":0,"footnotes":""},"categories":[2231,1864,179],"tags":[],"magazine-issues":[],"coauthors":[44],"class_list":["post-95125","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health-well-being","category-pharm","category-uconn-health"],"pp_statuses_selecting_workflow":false,"pp_workflow_action":"current","pp_status_selection":"publish","acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-05-28 11:50:03","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/95125","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/users\/12"}],"replies":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/comments?post=95125"}],"version-history":[{"count":5,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/95125\/revisions"}],"predecessor-version":[{"id":95226,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/95125\/revisions\/95226"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media\/88751"}],"wp:attachment":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media?parent=95125"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/categories?post=95125"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/tags?post=95125"},{"taxonomy":"magazine-issue","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/magazine-issues?post=95125"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/coauthors?post=95125"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}