Candida glabrata binds to glycosylated and lectinic receptors on the coronary endothelial luminal membrane and inhibits flow sense and cardiac responses to agonists.
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 and agonists. Because of the lectinic-oligosaccharide nature of CG binding, we tested the ability of CG to alter the agonist- and flow-induced changes in cardiac function in isolated perfused guinea pig hearts. Both transmission and scanning electron microscopy showed strong attachment of CG to the coronary endothelium, even after extensive washing. CG shifted the coronary flow vs. auricular-ventricular (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. Western blot analysis was used to determine binding of CG to isolated coronary endothelial luminal membrane (CELM) receptors, and the results indicate that flow-sensitive CELM receptors, ANG II type I, α-adrenergic 1A receptor, endothelin-2, and VCAM-1 bind to CG. In addition, CG inhibited agonist-induced effects of bradykinin, angiotensin, and phenylephrine on AV delay, coronary perfusion pressure, and left ventricular pressure. Mannose reversed the inhibitory effects of CG on the agonist responses. These results suggest that CG directly binds to flow-sensitive CELM receptors via lectinic-oligosaccharide interactions with mannose and disrupts the lectin-oligosaccharide binding necessary for flow-induced cardiac responses.
Escuela de Medicina, Unidad Académica Multidisciplinaria Zona Huasteca, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México david.tirado@uaslp.mx.
David
D
Torres-Tirado
Biology, West Chester University, West Chester, Pennsylvania; and.
Maureen
M
Knabb
Departamento de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, México;
Irene
I
Castaño
Departamento de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, México;
Araceli
A
Patrón-Soberano
Departamento de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, México;
Alejandro
A
De Las Peñas
Departamento de Fisiología, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México;
Rafael
R
Rubio
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D041221:Candida glabrata / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D002177:Candidiasis / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D002462:Cell Membrane / Q000378:metabolism* / Q000382:microbiology / Q000648:ultrastructure; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology / Q000648:ultrastructure; D042783:Endothelial Cells / Q000378:metabolism* / Q000382:microbiology / Q000648:ultrastructure; D006031:Glycosylation; D006168:Guinea Pigs; D054884:Host-Pathogen Interactions; D000067268:Isolated Heart Preparation; D008358:Mannose / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D009200:Myocardial Contraction; D010656:Phenylephrine / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure
D044140:Receptor, Angiotensin, Type 1; D018340:Receptors, Adrenergic, alpha-1; D017466:Receptors, Endothelin; D043562:Receptors, G-Protein-Coupled; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D010656:Phenylephrine; D008358:Mannose; D001920:Bradykinin
GPCR receptors; cell-cell interaction; flow sensors; lectins; oligosaccharides