Navigation Links
Understanding antibiotic resistance using crystallography and computation
Date:11/9/2012

Increasingly, bacteria such as E. coli are resisting the action of carbapenems by producing enzymes (carbapenemases) that break a specific chemical bond in the antibiotic, destroying its antimicrobial activity.

Carbapenemases are members of the group of enzymes called beta-lactamases that break down penicillins and related antibiotics, but it has not been clear why carbapenemases can destroy carbapenems while other beta-lactamases cannot.

Using molecular dynamics simulations, Professor Adrian Mulholland in the School of Chemistry and Dr Jim Spencer in the School of Cellular and Molecular Medicine, showed how a particular type of carbapenemase enzyme reorients bound antibiotic to promote its breakdown and render it ineffective.

Professor Mulholland said: "The class of antibiotics called carbapenems, drugs related to penicillin, are increasingly important in healthcare as treatments for bacterial infections. Until recently, carbapenems were 'antibiotics of last resort' but the growing problem of resistance to other drugs in organisms like E. coli (the leading cause of bloodstream infections in the U.K.) means that carbapenems are now becoming first-choice antibiotics for these infections. This is a worry because there are very few other treatment options for these organisms. Few new antibiotics effective against these pathogens are reaching the clinic.

"The recent appearance and spread of bacteria that resist carbapenems is a serious and growing problem: potentially, we could be left with no effective antibiotic treatments for these infections. The emergence of bacteria that resist carbapenems is therefore very worrying."

In a study published in the Journal of the American Chemical Society (JACS), the scientists combined laboratory experiments with computer simulations to investigate how one particular type of carbapenemase recognises and breaks down antibiotics.

Using X-ray crystallography, they obtained two 'snapshots' of the carbapenemase in the act of breaking down a carbapenem antibiotic. This static structural information was used as a starting point for simulations that modelled the motions of the enzyme and the bound antibiotic.

The simulations showed how the carbapenemase reorients the drug to promote its breakdown. In beta-lactamases that cannot break down carbapenems, this rearrangement cannot happen, and so the enzyme cannot break down the antibiotic. Knowing this should help in designing new drugs that can resist being broken down.

Dr Spencer said: "Combining laboratory and computational techniques in this way gave us a full picture of the origins of antibiotic resistance. Our crystallographic results provided structures which were the essential starting point for the simulations and the simulations were key to understanding the dynamic behaviour of the enzyme-bound drug.

"Identifying the molecular interactions that make an enzyme able to break down the drug, as we have done here, is an important first step towards modifying the drug to overcome bacterial antibiotic resistance."


'/>"/>
Contact: Hannah Johnson
hannah.johnson@bristol.ac.uk
001-179-288-896
University of Bristol
Source:Eurekalert

Related medicine news :

1. Researchers gain better understanding of mechanism behind tau spreading in the brain
2. Understanding and promoting mental health - Insights from psychological science
3. Understanding the links between inflammation and chronic disease
4. Cedars-Sinai researchers, with stem cells, advance understanding of spinal muscular atrophy
5. Discovery improves understanding of early onset inflammatory disease
6. Understanding flirtation in negotiation, shooter bias, love during marriage, and more
7. Wayne State develops better understanding of memory retrieval between children and adults
8. Studies seek better understanding and treatment of depression
9. Researchers closer to understanding actions of cells involved in atherosclerosis
10. Advancing understanding of treatment through clinical trials
11. Antibiotics Linked to Retinal Detachment Risk
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/12/2017)... ... October 12, 2017 , ... CitiDent and San Francisco dentists, ... cutting-edge Oventus O2Vent technology. As many as 18 million Americans are estimated to ... breathing. Oral appliances can offer significant relief to about 75 percent of people ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... ... products to meet the demand of today’s consumer and regulatory authorities worldwide. From ... probiotic experts and tested to meet the highest standard. , These products ...
(Date:10/12/2017)... ... October 12, 2017 , ... The American College of Medical Informatics (ACMI) will ... during the Opening Session of AMIA’s Annual Symposium in Washington, D.C. AMIA’s Annual ... F. Collen, a pioneer in the field of medical informatics, this prestigious award is ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... ... drug delivery system that we intend to develop to enable prevention of a ... lead to severe hearing loss, especially in pediatric patients. For cisplatin, hearing loss ...
(Date:10/12/2017)... ... ... HMP , a leader in healthcare events and education, today announced that ... ‘Best B-to-B Healthcare Website.’ Winners were announced during the Eddie & Ozzie Awards luncheon ... editorial and design excellence across a range of sectors. This year’s program included the ...
Breaking Medicine News(10 mins):
(Date:10/2/2017)... 2017 Diplomat Pharmacy, Inc. (NYSE: ... Consulting, LLC , and named its founder as Diplomat,s ... Tennessee , will operate under Diplomat ... service offerings for health care partners to include IT ... "In an interoperable world, technology delivers comprehensive ...
(Date:9/28/2017)... Hill-Rom Holdings, Inc. (NYSE: HRC), will host ... webcast on Friday, November 3, 2017, beginning at 7:00 ... approximately 8:30 a.m. (CDT) / 9:30 a.m. (EDT). ... performance and guidance for 2018, Hill-Rom executives will also ... performance, and long-range financial outlook through 2020. ...
(Date:9/25/2017)... , Sept. 25, 2017  EpiVax, Inc., a ... design, and immune-engineering today announced the launch of ... development of personalized therapeutic cancer vaccines. EpiVax has ... exclusive access to enabling technologies to the new ... will lead EpiVax Oncology as Chief Executive Officer. ...
Breaking Medicine Technology: