A novel target for therapeutics against Staph infection

Nov 28, 2008

Researchers at the Texas A&M Health Science Center Institute of Biosciences and Technology, and the University of Edinburgh have uncovered how a bacterial pathogen interacts with the blood coagulation protein fibrinogen to cause methicillin-resistant Staphylococcus aureus (MRSA) infections, a finding that could aid in developing therapeutics against the potentially deadly disease. Their work appears November 28 in the open-access journal PLoS Pathogens.

Once occurring more commonly in healthcare facilities, but now affecting segments of the general population, MRSA is a bacterial pathogen responsible for a range of diseases from mild skin infection to life-threatening sepsis. Even with antibiotics, these infections can still be fatal.

Senior author Magnus Höök, Ph.D. and his colleagues carried out biochemical and structural studies to determine the binding mechanism of clumping factor A (ClfA), a surface protein that plays an important role in the pathogenesis of S. aureus. The group found that ClfA binds to the blood-clotting protein fibrinogen (Fg) at a site that is also responsible for inducing platelet activation and thrombosis (clot inside a blood vessel).

The results show significant structural differences in how staphylococcal and platelet receptor proteins recognize fibrinogen. By exploiting this difference in recognition, the researchers show that agents could be designed that inhibit the ClfA–Fg interaction but do not interfere with the interaction of Fg with the platelet integrin, therefore avoiding unwanted side effects on the circulatory system.

Citation: Ganesh VK, Rivera JJ, Smeds E, Ko Y-P, Bowden MG, et al. (2008) A Structural Model of the Staphylococcus aureus ClfA–Fibrinogen Interaction Opens New Avenues for the Design of Anti-Staphylococcal Therapeutics. PLoS Pathog 4(11): e1000226. doi:10.1371/journal.ppat.1000226
dx.plos.org/10.1371/journal.ppat.1000226

Source: Public Library of Science

Explore further: English foxes safe for now as Cameron backs down

Related Stories

Faster, safer method for producing stem cells

Dec 04, 2012

A new method for generating stem cells from mature cells promises to boost stem cell production in the laboratory, helping to remove a barrier to regenerative medicine therapies that would replace damaged ...

Drug mitigates toxic effects of radiation in mice

Jun 23, 2010

While radiation has therapeutic uses, too much radiation is damaging to cells. The most important acute side effect of radiation poisoning is damage to the bone marrow. The bone marrow produces all the normal blood cells, ...

Recommended for you

English foxes safe for now as Cameron backs down

4 hours ago

English foxes won a temporary respite after Prime Minister David Cameron's promise to repeal a ban on hunting them failed to make it into his programme outlined in the Queen's Speech on Wednesday.

Sex chromosomes—why the Y genes matter

4 hours ago

Several genes have been lost from the Y chromosome in humans and other mammals, according to research published in the open access journal Genome Biology. The study shows that essential Y genes are rescue ...

How longhorned beetles find Mr. Right

5 hours ago

A longhorned beetle's sexy scent might make a female perk up her antennae. But when the males of several species all smell the same, a female cannot choose by cologne alone.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.