Adherence and penetration of vascular endothelium by Candida yeasts

Abstract

Metastatic infection after hematogenous dissemination of Candida species is presumably dependent on the fungus traversing the vascular endothelium. An in vitro model of the earliest events of metastatic Candida infection was developed with whole vascular strips. Freshly obtained porcine blood vessels were secured in a perforated Lucite template that allowed the application of yeasts directly to the endothelial surface. Multiple wells allowed experimental and control observations on the same vascular segments. Adherence to endothelium was greatest with Candida albicans and Candida tropicalis, less with Candida krulsei, and least with Candida parapsilosis, Candida pseudotropicalis, and Torullopsis glabrata. This hierarchy of adherence parallels that in other in vitro systems employing mucosal epithelial. cells or fibrin-platelet matrixes and reflects the known virulence of the respective species and their potential for hematogenous dissemination. C. albicans and C. tropicalis yeasts that adhered were capable of directly traversing the endothelial surface before the production of germ tubes. Heat or Formalin-killed yeasts and viridans group streptococci, although adherent, were incapable of vascular penetration, a process presumably attributable to enzymatic digestion of host tissue. Loss of integrity of penetrated endothelial tissue was verified by loss of dye exclusion, lactic dehydrogenase release, and ultramicroscopic changes. These two steps, adherence and penetration, provide direct insight into the earliest events in hematogenous Candida species dissemination and suggest that C. albicans and C. tropicalis yeasts are capable of initiating tissue invasion before germ tubes have had the opportunity to form and participate in the invasive process.

The adherence of Candida yeasts to human and bovine vascular endothelium and subendothelial extracellular matrix

“…It was first determined that C. albicans was inherently the most adherent yeast species (Table 1). A similar hierarchy of adherence of yeasts to endothelium has been shown by myself [1] and Rotrosen et al [2]. Since C. albicans was the most adherent species, only it was used in the remaining experiments.…”

“…This interaction has been previously addressed in two models. In one model, ex vivo porcine aortic strips were inoculated with large numbers of Candida yeasts which adherence to endothelial surfaces, primarily to the junctions between endothelial cells [1]. Furthermore, coadherence of yeasts to one another was a prominent feature of this model.…”

The contribution of electrostatic forces to the process of adherence of Candida albicans yeast cells to substrates

“…Previous work has established that formaldehyde-treated yeast cells do not adhere as well as viable untreated yeast cells to ex vivo porcine endothelium [7]. If formaldehyde treatment in-260 creases the net negative charge on the surface of cells as has been claimed [5] then treating the endothelium with formaldehyde should reduce the adherence of viable untreated yeast cells to this tissue as well.…”

“…Previous work by us has established that altering the electrostatic charges on the surface of C. albicans will affect the adherence of yeast cells to underlying substrates. For example, treating yeast cells with formaldehyde increases the net negative surface charge on the microorganism [5] and markedly reduces the number of yeast cells which adhere to the surface of ex vivo porcine endothelium [7]. In addition formaldehyde-treated yeast cells demonstrate a 49% reduction in adherence to a plastic surface, whereas carbodiimide-treated yeast cells which are more positively charged demonstrate a 72% increase in adherence to a plastic surface [5].…”

Interactions of Candida albicans with other Candida spp. and bacteria in the biofilms*

“…Candida spp. such as T. glabrata (Hawser 1996), C. parapsilosis (Klotz et al 1983), C. guilliermondii (Maisch and Calderone 1980) and C. krusei exhibit a similar degree of adherence as C. albicans.…”