Candida species are the most common fungal pathogens isolated from the oral cavity. Their oral existence both as a commensal and an opportunist pathogen has intrigued clinicians and scientists for many decades, and recent investigations have revealed many attributes of this fungus contributing to its pathogenicity. In addition, the advent of the human immunodeficiency virus infection and AIDS has resulted in a resurgence of oral Candida infections. Clinicians are witnessing not only classic forms of the diseases but also newer clinical variants such as erythematous candidosis, rarely described hithertofore. Therefore, this review is an attempt at detailing the current knowledge on Candida and oral candidoses together with the newer therapeutic regimes employed in treating these mycoses.

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Candida and Oral Candidosis: A Review

The gene ECE1 (extent of cell elongation 1) was isolated by differential hybridization screening of a Candida albicans cDNA library by using probes derived from populations of yeast cells or hyphae. Expression of this gene was not detected when C. albicans grew as a budding yeast cell but was observed within 30 min after cells had been induced to form hyphae. In all strains tested, regardless of the induction signal, ECE1 expression correlated with the extent of cell elongation. The genomic version of ECE1 was cloned and sequenced. The deduced 271-amino-acid polypeptide consisted of eight tandem repeats of a degenerate 34-amino-acid sequence which contained no discernible homology with other known sequences. An ECE1 null mutant displayed no morphological alterations, which demonstrated that ECE1 is not essential for cell elongation or hypha formation despite the strict morphological association of its expression.

https://iai.asm.org/content/iai/61/9/3648.full.pdf

Cloning and characterization of ECE1, a gene expressed in association with cell elongation of the dimorphic pathogen Candida albicans

This review will survey environmental controls on the morphology of Candida albicans, describe the cellular and ultrastructural events associated with morphological transitions in this fungus, and attempt to relate biochemical phenomena that have been reported to be associated with dimorphic change to C albicans cell biology The synthesis of the cell wall of C albicans and its control remain largely undiscovered, but it is clear that the cell wall is the principal component involved in shape determination Possible models for C albicans dimorphism will be critically reviewed

Morphogenesis in Candida Albicans

Two chemically mutagenized agerminative variants of Candida albicans were used to immunize mice against challenge with highly virulent cells of the parent strain. Although both mutants (Vir- 3 and Vir- 13) resulted in nonlethal infection and could be recovered from mouse organs for many days after the intravenous inoculation of 10(7) to 10(6) cells, significant protection to systemic challenge with virulent C. albicans was induced by only one (Vir- 3) of the two variants. Anticandidal resistance in Vir- 3-infected mice was associated with the occurrence in vivo of strong delayed-type hypersensitivity to Candida antigen, detection in vitro of highly fungicidal effector macrophages, and presence in the serum of a large proportion of Candida-reactive antibodies of the immunoglobulin G2a isotype. Bulk cultures of purified CD4+ lymphocytes from mice infected with either mutant were compared for their ability to produce gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-6 in vitro. After stimulation with specific antigen, CD4+ cells from Vir- 3-immunized mice released large amounts of the Th1-specific cytokines, IFN-gamma and IL-2, at a time when CD4+ cells from Vir- 13-infected mice predominantly secreted the characteristic Th2 cytokines, IL-4 and IL-6. These results were confirmed by quantitative analysis of cytokine-producing Th1 and Th2 cells. In addition, only mice infected with Vir- 3 displayed a high frequency of CD8+ cells with the potential for in vitro lysis of yeast-primed bone marrow macrophages. Purified CD4+ cells from Vir- 3-infected mice, but not a mixture of these cells with CD4+ lymphocytes from mice infected with Vir- 13, could adoptively transfer delayed-type hypersensitivity reactivity onto naive mice. Taken together, these data suggest that both Th1 and Th2 CD4+ lymphocytes may be activated during experimental C. albicans infection in mice.

https://iai.asm.org/content/iai/59/12/4647.full.pdf

Th1 and Th2 cytokine secretion patterns in murine candidiasis: association of Th1 responses with acquired resistance.

Publisher Summary Simple (steady-state) models can aid in the interpretation of radioactive tracer data, provide information on reaction rates in vivo , and make predictions about intracellular and intercellular compartmentation. More complex (transition) models can be used to integrate, over time, data on enzyme mechanisms, metabolite concentrations, and flux. These models can help define those events, which are most critical to a particular metabolic transformation, for example, in development, aging, malignancy, dimorphic fungi, or a fermentation process. The modeling approach is also useful in the analysis of specific areas of metabolism in higher animals, for example, glycogen metabolism in liver or glycolysis in the perfused heart. This chapter summarizes the data required for and the kind of information obtained from a steady state model and compares these to a transition model.

The modeling approach.

SUMMARY: The growth characteristics of Candida albicans CM145,348 have been examined under aerobic conditions in continuous culture. At different steady states the environment was controlled with respect to the concentrations of dissolved oxygen, carbon and nitrogen, the pH, and the temperature. Dry matter, substrate concentration, yield, specific oxygen uptake, specific carbon dioxide release and respiration quotient were examined as a function of the dilution rate. The morphology depended on the carbon source. Maltose produced a mycelial morphology, whereas with lactate a yeast culture was obtained. With fructose or glucose as a carbon source a mixed morphology of yeast, pseudo-mycelial and mycelial forms was produced. A large number of different growth conditions were examined in batch culture but a mixed morphology was always obtained.

M. G. Shepherd

Papers

The Production and Growth Characteristics of Yeast and Mycelial Forms of Candida albicans in Continuous Culture