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.
PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.plos.org/10.1371/journal.ppat.1000226 (link will go live on Friday, November 28)
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
Texas A&M Health Science Center
Institute of Biosciences and Technology
Senior Communications Specialist
Marketing and Communications
Texas A&M Health Science Center
979 458 0770
This press release refers to an upcoming article in PLoS Pathogens. The release is provided by the article authors and their institutions. Any opinions expressed in these releases or articles are the personal views of the journal staff and/or article contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the releases and articles and your use of such information.
About PLoS Pathogens
PLoS Pathogens (www.plospathogens.org) publishes outstanding original articles that significantly advance the understanding of pathogens and how they interact with their host organisms. All works published in PLoS Pathogens are open access. Everything is immediately available subject only to the condition that the original authorship and source are properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.