Candida glabrata prevents flow‐dependent cardiac effects through lectinic interaction with coronary endothelial luminal membrane receptors (696.8)

Abstract

Candida glabrata (CG) is an opportunistic fungal pathogen that initiates infection by binding to host cells via specific lectin‐like adhesin proteins. We have previously shown the importance of lectin‐oligosaccharide binding in cardiac responses to flow. Due to the lectinic nature of CG binding, we tested the ability of CG to alter the flow‐induced changes in cardiac function in isolated perfused guinea pig hearts. Binding of CG to isolated coronary endothelial luminal membrane (CELM) receptors was determined by Western blot. CG shifted the coronary flow versus AV‐delay relationship upward, indicating that greater flow was required to achieve the same AV delay. This effect was completely reversed with mannose, partially reversed with galactose and N‐ acetylgalactosamine, but hyaluronan had no effect. In addition, mannose reversed the inhibitory effects of CB on AV delay, coronary perfusion pressure and left ventricular pressure. Western blot results indicate that flow sensitive CELM receptors, ET‐2, Ang I, VCAM‐1, and α‐ adrenergic, bind to CG. We propose that CG directly binds to flow sensitive CELM receptors via lectinic interactions with mannose and disrupts the lectin‐oligosaccharide binding necessary for flow‐induced cardiac responses.Grant Funding Source: Supported by grant of CONACYT CB‐2008/101850