Selection and pathogenicity of Candida albicans in HIV infection

Abstract

The progression of immune‐suppression due to infection with HIV is mirrored by an increase in the severity and prevalence of oral candidosis. The transition of C. albicans from harmless commensal to unrelenting pathogen in the susceptible host is a fine line attributable to an extensive repertoire of selectively expressed virulence determinants, including hyphal formation, thigmotropism, protease secretion, adherence and phenotypic switching. The transition from commensal to pathogen has been linked to the formation of elongated hyphae which may more readily penetrate epithelial surfaces. Invasion may be enhanced by thigmotropism which enables hyphae to sense intercellular junctions and surface discontinuities in order to find areas that may be more readily breached. Electron micrograph studies suggest that C. albicans are able to penetrate mucosal tissues by secreting hydrolytic enzymes at the tip of the invading hyphae. Recent studies have shown that protease secretion is upregulated in C. albicans isolated from AIDS patients. Similarly, the propensity for C. albicans to adhere to oral mucosa appears to be enhanced in isolates from HIV‐infected subjects. These two virulence determinants may be coordinately regulated and DNA fingerprinting studies suggest that these phenotypic alterations may be associated with the selection of C. albicans with altered genotypes. The mechanisms by which hypervirulent C. albicans may be selected in HIV‐infected patients is likely to be a multifactorial process associated with the pathobiological effects of HIV infection and to the increased candidal proliferation so evident in these patients.

Yeasts in Apical Periodontitis

“…The main adhesin molecules of C. albicans responsible for adhesion to host cells seem to be cell wall mannoproteins (Sweet, 1997). However, several other factors also contribute to the adherence of yeasts, e.g., cell-surface hydrophobicity, environmental pH, and concentrations of iron, calcium, zinc, and carbon dioxide (Ener and Douglas, 1992;Klotz, 1994;Samaranayake et al, 1995;Sohnle et al, 2001).…”

“…The transition of C. albicans from a harmless commensal to a pathogenic organism appears to be dependent on minor changes in predisposing conditions which cause the expression of a variety of virulence factors (Shepherd, 1992;Sweet, 1997). These factors include adherence, hyphal formation, thigmotropism, protease secretion, and phenotypic switching phenomenon.…”

“…Although hyphal formation is not a prerequisite for pathogenicity of C. albicans, biopsies of candidal infections often reveal hyphal adherence to and penetration through epithelial tissues, indicating increased pathogenicity in comparison with ovoid yeast forms (Sweet, 1997). It seems that the hyphal penetration into tissues is enhanced by thigmotropism, i.e., contact sensing by hyphae to find intracellular junctions or microscopic breaks on mucosal surfaces (Sherwood et al, 1992;Gow et al, 1994;Sweet, 1997). One of the key virulence determinants of Candida species is their ability to produce and secrete aspartyl proteases which digest a variety of host proteins.…”

“…This genetically controlled phenomenon is known as phenotypic switching, and it may occur relatively frequently, especially under stress (Soll, 1988). Phenotypic switching may assist in survival of and colonization by the yeasts, and it may also lead to genetic selection of adaptive strains (Sweet, 1997). Virulence factors and their possible contributions to apical periodontitis are listed in Table 1.…”

“…The ability of C. albicans to grow into dentin indicates expression of several virulence factors in necrotic root canals: hyphae formation, thigmotropism, and secretion of proteolytic enzymes (Kaminishi et al, 1986;Hagihara et al, 1988;Sweet, 1997;Naglik et al, 1999). Therefore, the invasion of the dentinal tubules by candidal pseudohyphae resembles the penetration of hyphae deep into the epithelium in cases of acute pseudomembranous candidosis (Kinirons, 1983).…”