Candida albicans—do mycelia matter?

Abstract

Growth of Candida albicans in the mycelial phase is neither necessary for initiation of infection in the kidney of the mouse, following intravenous inoculation, nor for the establishment of chronic renal colonization. However, mycelial formation would appear to be important in the establishment of pelvic lesions with their associated pathological changes. Two mycelia-less mutants, CA-2 and MM2002, in the early stages of infection tended to develop in the glomeruli of the mouse kidney cortex while the wild-type parent strains spread throughout the cortex and medulla, with only occasional involvement of glomeruli. The mutants appeared to stimulate a milder inflammatory response than the parent strains. In chronic infections with wild-type strains, tangled masses of mycelia filled the renal pelvis, but pyelonephritis and hydronephrosis did not depend on a persistent cortical infestation. Yeasts of the mutant strains persisted in the body of the kidney and stimulated a continuing neutrophil response. Systemic infections with wild-type strains were eliminated by treatment with low doses of an azole antifungal drug, ICI 195,739, or with amphotericin B, whereas systemic infections with the mutant strains were much reduced, but not eliminated, by relatively high doses of either of the two drugs. Unlike azole drugs, amphotericin B does not show differential activity against the two morphological forms of C. albicans. Because kidney infections with the mutant strains are relatively resistant to amphotericin B as well as the azole tested, we conclude that the impressive activity of azoles in vivo may not be explained entirely by their inhibition of mycelial growth.Following intravenous (IV) inoculation of mice with Candida albicans, yeasts can be recovered from a variety of internal organs, although their numbers decrease with time. Progressive infection is observed only in the kidney [8,14] and this progression is associated with passage of the fungus through the wall of both cortical and medullary tubules or glomerular tufts into the lumen of the nephrons. Growth in this apparently protected site is not associated with the inflammatory response which is so prominent in the interstitium [8]. After forming long pseudohyphae within the renal tubular lumen, the fungus penetrates back into the renal parenchyma. This reinvasion of the interstitium is followed by a marked polymorphonuclear response and the development of large abcesses [7]. Winblad [18] confirmed this progression and

Growth and guidance of the fungal hypha

“…While some histological sections of diseased tissues are virtually free from hyphal cells other studies suggest that hyphae are better able to gain a foothold in the primary invasion of a host tissue (Martin et al, 1984;Sobel e t al., 1984). Experiments using animal models and strains that are debilitated in hyphal formation have shown that the yeast cells are undoubtedly pathogenic in their own right (Simonetti & Strippoli, 1973;Shepherd, 1985;Ryley & Ryley, 1990) but equivalent hyphal-competent strains penetrate more deeply into the host tissues (Ryley & Ryley, 1990). From a teleological point of view tip-growing hyphae would seem well adapted for penetration of surfaces such as epithelia and it is with that in mind that we have looked for behavioural adaptations of the germ tube when grown in contact with a surface.…”

Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene

“…Dimorphic growth, the ability to grow in more than one form, is believed to contribute to the pathogenicity of C. albicans (Corner and Magee, 1997). Mutant strains that are defective in switching between ®lamentous growth and budding growth frequently exhibit reduced virulence (Sobel et al, 1984;Shepherd, 1985;Ryley and Ryley, 1990;Leberer et al, 1997). Recently, a well-de®ned mutant strain with a profound defect in ®lamentous growth was shown to be avirulent after intravenous inoculation of mice (Lo et al, 1997a).…”

Candida Albicans has a Cell-Associated Ferric-Reductase Activity which is Regulated in Response to Levels of Iron and Copper

“…This fungus is a common commensal of the gut, mouth and vagina, but under certain circumstances it can cause both superficial infections, and in the case of immunocompromised patients, serious systemic infections (Odds, 1987). It is thought that both the yeast and hyphal forms of C. albicans can be pathogenic (Kerridge, 1993;Ryley & Ryley, 1990). Investigations concerning C. albicans iron acquisition and uptake have to date been limited.…”