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:4/25/2017)... ... April 25, 2017 , ... Back Pain Centers ... back pain with a reputable physician in their area, announces the launch of a ... information for patients who are looking for reputable physicians to help them with back ...
(Date:4/25/2017)... ... , ... There is no better place in South Florida to undergo two ... May issue of Consumer Reports focused on heart health. , The magazine gave ... after coronary bypass and aortic valve replacement procedures. , Consumer Reports rated ...
(Date:4/24/2017)... Nashville, TN (PRWEB) , ... April 24, 2017 , ... ... electrifying fans and transforming the quarterback position. The former overall number one pick in ... his professional football career. He holds the record for the most career rushing yards ...
(Date:4/24/2017)... , ... April 24, 2017 , ... The bar for ... those unreal icons inhabiting the rarified air of pop and film stardom.(1) Not to ... anyone snapping pictures: the smile. Grins now run the gamut from being encrusted with ...
(Date:4/24/2017)... ... ... The John P. McGovern Museum of Health and Medical Science is now partnered with ... share results with their physicians. Members and guests can sign up for its free ... Dr. David Eagleman, formerly at Baylor College of Medicine and now at Stanford University, ...
Breaking Medicine News(10 mins):
(Date:4/19/2017)... , April 19, 2017 ... an immune response in pets such as canine, ... are of various types such as Attenuated Live ... Vaccines, DNA Vaccines and Recombinant Vaccines. Attenuated live ... virus or bacteria, which have been weakend under ...
(Date:4/18/2017)...  Cardinal Health (NYSE: CAH ) today ... per share (EPS) guidance and providing a preliminary view ... with this morning,s announcement of the planned acquisition of ... businesses. Cardinal Health now believes that fiscal ... the bottom of its previous guidance range of $5.35 ...
(Date:4/18/2017)... 18, 2017  Astute Medical, Inc., developer of biomarkers ... be presented at the 2017 National Kidney Foundation (NKF) ... continues through April 22. Physicians will present data on ... assess risk for acute kidney injury (AKI) during the ... Elevated levels of TIMP-2 and IGFBP-7 ...
Breaking Medicine Technology: