Candida glabrata binds to glycosylated and lectinic receptors on the coronary endothelial luminal membrane and inhibits flow sense and cardiac responses to agonists
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 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.
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The C. glabrata Cgsir3Δ mutant displays mannose- and galactose-dependent strong binding to the coronary endothelium through coronary endothelial luminal membrane lectinic GPCRs including endothelin-2 and α-adrenergic 1A receptor, leading to altered cardiac functions.
“The C. glabrata Cgsir3Δ mutant, which expresses higher levels of Epa adhesins [36], has been reported to display mannose- and galactose-dependent strong binding to the coronary endothelium, through the coronary endothelial luminal membrane lectinic G protein-coupled receptors (GPCRs) including endothelin-2 and α-adrenergic 1A receptor, that led to altered cardiac functions [139].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [139]
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- Authors
- Torres-Tirado, D., Knabb, M., Castaño, I., Patrón-Soberano, A., De Las Peñas, A., & Rubio, R.
- Affiliations
- Escuela de Medicina, Unidad Académica Multidisciplinaria Zona Huasteca, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México
- West Chester University (US)
- Institute for Scientific and Technological Research (MX)
- Departamento de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, México;
- Autonomous University of San Luis Potosí (MX)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2016-01-01
- Volume
- 310
- Issue
- 1
- Pages
- R24-R32
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2293048151
- Cited by
- 10
- References
- 43
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- PROMEP 2014. Programa Para El Mejoramiento del Profesorado (UASLP-PTC-514)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Epidemiology › Infective Endocarditis Diagnosis and Management
- Keywords
- Candida glabrata, fungal adhesion, coronary endothelium, mannose, galactose, N-acetylgalactosamine, angiotensin II type 1 receptor, endothelin-2, VCAM-1, bradykinin, angiotensin, phenylephrine, coronary perfusion pressure, left ventricular pressure
- MeSH terms
- Isolated Heart Preparation, Angiotensin II, Animals, Bradykinin, Candidiasis, Cell Membrane, Coronary Circulation, Coronary Vessels, Glycosylation, Guinea Pigs, Mannose, Microscopy, Electron, Scanning, Mutation, Myocardial Contraction, Phenylephrine, Ventricular Function, Left, Receptors, Endothelin, Ventricular Pressure, Receptors, Adrenergic, alpha-1, Vascular Cell Adhesion Molecule-1, Candida glabrata, Endothelial Cells, Receptors, G-Protein-Coupled, Receptor, Angiotensin, Type 1, Microscopy, Electron, Transmission, Host-Pathogen Interactions
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