Pathogenesis of vaginal candidiasis: studies with a mutant which has reduced ability to adherein vitro

Abstract

A spontaneous, cerulenin-resistant mutant of Candida albicans (strain 4918-10) was found to adhere less readily to human vaginal mucosal cells in vitro than a wild type C. albicans (strain 4918). In a murine model of vaginal infection, strain 4918-10 was found to be less virulent than wild type C. albicans, i.e., the infection rate caused by 4918-10 was only 31% of that observed with wild type, 4918. A chitin-soluble extract (CSE) prepared from 4918 blocked attachment of yeast cells to human vaginal epithelial cells, while CSE from 4918-10 did not significantly reduce the attachment of yeasts to vaginal cells. Both 4918 and 4918-10 produced hyphae in vitro and in vivo, were negative for proteinase production and grew equally well at 28"C and 37"C. The data suggest that adherence to vaginal mueosa may be an important determinant in the pathogenesis of vaginal infection eaused by C. albicans.The attachment of Candida albicans yeast cells in vitro to human vaginal mucosa epithelial (VME) cells has been described by several investigators [4,[7][8][9][12][13][14][15][16][17]. Attachment of yeast cells to human VME cells in vitro was reduced if yeast cells were killed by UV irradiation, formalin or treated with proteinases (but not pepsin). Adherence was not influenced by pH [7] or if yeast cells were pretreated with salts or divalent cations, detergents, urea, lipase or a-mannosidase [8]. However, fl-mercaptoethanol did reduce adherence significantly [8].The nature of the surface component promoting yeast attachment to vaginal mucosa is not known. Lee & King [8] suggested that cell wall mannan-protein may be involved in attachment. Contrary to that, our previous studies revealed that chitin, chitin derivatives, a chitin soluble extract and amino sugars [9,12,13] blocked in-vitro adherence to human VME.Animal models have been used to study the pathogenesis of vaginal infection [9,13,15,18]. We have shown in a murine model of vaginal candidiasis that animals, pretreated with vaginal rinses consisting of a chitin-soluble extract (CSE) or N-acetyl-glucosamine, did not develop infection upon subsequent inoculation of C. albicans [9,13].

Sequence analysis and expression of the two genes for elongation factor 1 alpha from the dimorphic yeast Candida albicans

“…Furthermore, codon bias and the promoter and termination signals of the C. albicans EF-la proteins were remarkably similar to those of S. cerevisiae EF-la. Taken together, these results suggest that C. albicans is more closely related to the ascomycete S. cerevisiae than to the zygomycete M. racemosus.Candida albicans is a dimorphic fungal pathogen that acquires virulence and the ability to adhere to host tissues as it undergoes the transition from yeast to mycelial forms (26,27,37,45,61). The phylogenetic relationship of C. albicans to other fungi is uncertain because of the lack of a sexual cycle, resulting in its being placed in the form subdivision Deuteromycotina (Fungi Imperfecti) along with a diverse group of 15,000 other species (48).…”

“…Candida albicans is a dimorphic fungal pathogen that acquires virulence and the ability to adhere to host tissues as it undergoes the transition from yeast to mycelial forms (26,27,37,45,61). The phylogenetic relationship of C. albicans to other fungi is uncertain because of the lack of a sexual cycle, resulting in its being placed in the form subdivision Deuteromycotina (Fungi Imperfecti) along with a diverse group of 15,000 other species (48).…”

Adhesion ofCandida albicansmutant strains to host tissue

“…Thus, our in vitro studies on adhesion, a process considered a marker for virulence, are compatible with these in vivo data. Moreover, Lehrer et al [23] showed with a cerulenine‐resistant C. albicans mutant a correlation between in vitro adhesion ability and in vivo pathogenicity. The mutants, which adhered less in vitro to vaginal cells, were also less pathogenic in a murine experimental vaginitis model.…”

Adhesion of Candida albicans mutant strains to host tissue

“…Thus, our in vitro studies on adhesion, a process considered a marker for virulence, are compatible with these in vivo data. Moreover, Lehrer et al [23] showed with a cerulenine-resistant C. albicans mutant a correlation between in vitro adhesion ability The adhesion values relate to C.A. cells that adhere to 100 BEC.…”