Researchers at the University of Toronto have developed a therapy for a potentially deadly type of infection common in catheters, artificial joints and other "in-dwelling" medical devices. Their findings appear in the Open Access Journal PLoS Pathogens on September 8th.
The therapy targets fungal infections, which are hard to treat in such devices because they are composed of biofilms--complex groupings of cells that attach to surfaces. Biofilms, in turn, are coated in a gooey matrix that resists drugs.
Patients often undergo surgical removal of the infected catheter or other device in an attempt to clear the disease and prevent a system-wide dispersal of infecting cells.
In this study, researchers showed that inhibiting the function of a protein called Hsp90 abolishes drug resistance in the two main fungal pathogens of humans, Candida albicans and Aspergillus fumigatus. "It takes classic antifungals, which were not effective against biofilms, and makes them very effective," said Prof. Leah Cowen, principal investigator on the study who holds the Canada Research Chair in Microbial Genomics and Infectious Disease at U of T's Department of Molecular Genetics.
In an animal model of a central venous catheter infected with deadly fungus, the researchers were able to completely clear the infection by inhibiting Hsp90 and applying antifungals.
Fungal pathogens are a major clinical problem. Candida albicans is the third-leading cause of intravascular catheter-related infections, and is fatal in about 30% of infections associated with devices. And the number of acquired fungal bloodstream infections has increased by more than 200% over the last two decades, partly because successful treatments for previously fatal diseases like cancer and AIDS have left many patients immune-compromised and susceptible to infection.
With more than 10 million patients per year now receiving catheters, artificial joints and other devices, there is a pressing need for a better understanding of biofilms and their role in drug resistance of fungal pathogens.
FINANCIAL DISCLOSURE: N. R. was supported by a Natural Sciences & Engineering Research Council of Canada Graduate Scholarship and L.E.C. by a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund, by a Canada Research Chair in Microbial Genomics and Infectious Disease, and by Canadian Institutes of Health Research Grant MOP-86452. JLL-R acknowledges support of Public health Service grant numbered R21AI080930 from the National Institute of Allergy and Infectious Diseases. P.U. is supported by a postdoctoral fellowship, 10POST4280033, from the American Heart Association. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.
CITATION: Robbins N, Uppuluri P, Nett J, Rajendran R, Ramage G, et al. (2011) Hsp90 Governs Dispersion and Drug Resistance of Fungal Biofilms. PLoS Pathog 7(9): e1002257. doi:10.1371/journal.ppat.1002257
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Combination therapy rids common infection from implanted medical devices