The ultrastructure of Candida albicans infections

Scrapings of Candida albicans plaques from the tongue and buccal mucosa of patients with oral candidiasis were examined by electron microscopy. In addition, urine sediment from patients with infection of their catheterized urinary tracts was similarly examined. Three types of C. albicans-oral epithelial cell interactions were noted: a loose adherence apparently mediated by a ruthenium red positive matrix, a "tight" adherence where no space could be seen between the host and yeast cell. and invasion of host cells by yeast hyphal elements. Adhesion of Candida blastospores to hyphal elements and adhesion of bacteria to Candida cells was also frequently observed. Urine sediments from patients with mixed bacteria-yeast infections demonstrated adhesion of the bacteria to the yeast cells. This phenomenon was also demonstrated in in vitro experiments and fibrous ruthenium red material invariably occupied the zone of adhesion. Phagocytosis of yeast by polymorphonuclear leukocytes was found in urinary, but not in oral. candidiasis. Our in vivo and in vitro observations indicate that a ruthenium red positive matrix covers the surfaces involved in the yeast to yeast, yeast to host, and yeast to bacteria adhesion.     

Photodynamic inactivation for controlling Candida albicans infections

Antimicrobial photodynamic therapy (APDT) combines a non-toxic dye, termed photosensitizer, which is activated by visible light of appropriate wavelength which will produce reactive oxygen species (ROS). These ROS will react with cellular components inducing oxidative processes, leading to cell death. A wide range of microorganisms, have already showed susceptibility to APDT. Therefore, this treatment might consist in an alternative for the management of fungal infections that is mainly caused by biofilms, since they respond poorly to conventional antibiotics and may play a role in persistent infections. Biofilms are the leading cause of microbial infections in humans, thus representing a serious problem in health care. Candida albicans is the main type of fungi able to form biofilms, which cause superficial skin and mucous membrane infections as well as deep-seated mycoses, particularly in immunocompromised patients. In these patients, invasive infections are often associated with high morbidity and mortality. Furthermore, the increase in antifungal resistance has decreased the efficacy of conventional therapies. Treatments are time-consuming and thus demanding on health care budgets. Additionally, current antifungal drugs only have a limited spectrum of action and toxicity. The use of APDT as an antimicrobial topical agent against superficial and cutaneous diseases represents an effective method for eliminating microorganisms.     

Disruption of the intestinal mucosal barrier in Candida albicans infections

Candida albicans is a common microorganism in the intestine. However, invasive C. albicans infection has emerged as a life-threatening disease in recent years. The mortality rate of invasive candidiasis is high in critically ill hosts. C. albicans can switch from the yeast to the hyphal morphology, and take advantage of the impaired intestinal mucosal barrier and insufficient immunity of the host to facilitate its colonization and penetration. Despite the availability of potent new antifungal drugs in recent years, the treatment of severe candidiasis, especially candidaemia, has not been substantially improved. In this review, the virulence factors of C. albicans, as well as the antagonistic role of the intestinal mucosal barrier will be discussed to illuminate the mechanisms of C. albicans enterogenic infections.     

抗白念珠菌感染的疫苗及抗体研究进展

白念珠菌是与人类共生的条件致病真菌,能引起免疫力低下患者皮肤黏膜和全身系统性持续感染.系统性念珠菌病是引起免疫力低下患者死亡的主要原因之一.由于临床缺乏念珠菌病的早期诊疗手段、可用的抗真菌药物种类有限且毒副作用大、耐药菌株越来越普遍、新药研发难度大等因素,抗真菌治疗依然面临着严峻挑战.目前有较多研究者致力于阐明白念珠菌感染的宿主免疫应答机制,并试图研发抗白念珠菌感染的免疫治疗方法,使免疫治疗有望成为预防和治疗真菌感染的有效手段.该文将几种抗白念珠菌感染的疫苗和抗体研究进展作简要概述,旨在为新型抗白念珠菌感染疫苗及抗体的研究提供参考.     

Growth stimulation and inhibition of Candida albicans by metabolic by-products

Morphological mutants obtained from one strain ofCandida albicans were able to synthesize, from simple inorganic salts, glucose, and biotin a variety of complex organic molecules. The organic substances, detected in culture filtrates, were not identical for all the mutants or for the parental form from which they were derived. The substances were found to inhibit or stimulate cell growth, mycelium production, and also to influence the reductive and enzymatic abilities of other cells. Polysaccharides, proteins, nucleic acids, and DNA were detected in the extracellular medium.     

Toll-like receptor-2 is essential in murine defenses against Candida albicans infections

In this work, we studied the role of toll-like receptor-2 (TLR2) in murine defenses against Candida albicans. TLR2-deficient mice experimentally infected intraperitoneally (i.p.) or intravenously (i.v.) in vivo had very significant impaired survival compared with that of control mice. In vitro production of TNF-alpha and macrophage inhibitory protein-2 (MIP-2) by macrophages from TLR2-/- mice in response to yeasts and hyphae of C. albicans were significantly lower (80% and 40%, respectively; P <0.05) than production by macrophages from wild-type mice. This impaired production of TNF-alpha and MIP-2 probably contributed to the 41% decreased recruitment of neutrophils to the peritoneal cavity of i.p. infected TLR2-/- mice. In contrast, in vitro phagocytosis of yeasts and production of reactive oxygen intermediates (ROI) were not affected in macrophages from TLR2-/- animals. Our data indicate that TLR2 plays a major role in the response of macrophages to C. albicans, triggering cytokine and chemokine expression, and it is essential for in vivo protection against infection.     

Protection against systemic infections with various Candida species elicited by vaccination with Candida albicans ribosomes

This study investigated whether subcutaneous vaccination of mice with ribosomes from Candida albicans strain CBS 562 would also provide protection against infections by other isolates of Candida. Experiments with a total of 628 mice demonstrated that vaccination induced significant protection against heterologous C. albicans (serotypes A and B) and C. tropicalis isolates in terms of their 30 day survival rates. In all instances, however, protection was lower than that obtained against the homologous strain. In addition, a significant decrease in fungal colonization of the kidneys was found in immunized animals as compared to the non immunized controls. Cell-mediated immune responses against cytoplasmic extracts of the various fungi, as detected in vivo by the foot pad swelling test and in vitro by the lymphocyte transformation assay, were induced by the C. albicans ribosomal vaccination. The results show it is possible to induce cross protection to various Candida species by immunization with C. albicans ribosomes.     

Gluconeogenesis in Candida albicans

According to different metabolic situations in various stages of Candida albicans pathogenesis the regulation of carbohydrate metabolism was investigated. We report the genetic characterization of all major C. albicans gluconeogenic and glyoxylate cycle genes (fructose-1,6-bisphosphatase, PEP carboxykinase, malate synthase and isocitrate lyase) which were isolated after functional complementation of the corresponding Saccharomyces cerevisiae deletion mutants. Remarkably, the regulation of the heterologously expressed C. albicans gluconeogenic and glyoxylate cycle genes was similar to that of the homologous S. cerevisiae genes. A C. albicans DeltaCafbp1 deletion strain failed to utilize non-fermentable carbon sources but hyphal growth was not affected. Our results show that regulation of gluconeogenesis in C. albicans is similar to that of S. cerevisiae and that the current knowledge on how gluconeogenesis is regulated will facilitate the physiological understanding of C. albicans.     

Karyotyping of Candida albicans and Candida glabrata isolates from recurrent vaginal infections by pulsed-field gel electrophoresis

In the present study, 16 women with recurrent vulvovaginal candidiasis (RVVC) due to Candida albicans and Candida (Torulopsis) glabrata were followed for a period of 4 to 12 months, and 36 vaginal isolates were evaluated by pulsed-field gel electrophoresis (PFGE). Eleven women were infected by C. albicans and 5 by C. glabrata. Three electrophoretic karyotypes of C. albicans and 3 of C. glabrata were identified throughout the follow-up. All patients but one was infected with the same karyotype of C. albicans or C. glabrata during the follow-up period. Two different karyotypes of C. glabrata were identified in one patient in the course of 12 months. The results confirmed the diversity of the karyotypes of C. albicans and C. glabrata causing vulvovaginitis, and demonstrated the persistence of colonization with the same strain over different periods of time despite therapy (15/16 women).     

Bidirectional stimulation of the white-opaque transition of Candida albicans by ultraviolet irradiation

Most strains of Candida albicans are capable of switching spontaneously and at high frequency between a number of phenotypes distinguishable by colony morphology. The switching frequency of Candida albicans strain WO-1 between two predominant phenotypes, 'white' and 'opaque', and a minor phenotype, 'fuzzy', increased dramatically with low doses of ultraviolet irradiation that killed less than 20% of the population. The ultraviolet irradiation effect continued to be expressed over many generations as evidenced by stimulated sectoring. Ultraviolet irradiation stimulated switching in both the white-to-opaque and opaque-to-white direction, suggesting that a common mechanism functions in both directions.     

Adhesins in Candida albicans.

The adherent properties of Candida albicans blastoconidia and germ tubes have long been appreciated, but little is known about the mechanisms responsible for adherence. Recently, three genes, ALA1, ALS1 and HWP1, encoding proteins with adherent properties and motifs consistent with linkage to the beta-1, 6-glucan of C. albicans cell walls have provided insight into the topology of protein adhesins. Hwp1, a developmentally regulated adhesin of germ tubes and hyphae, attaches to buccal epithelial cells by an unconventional, transglutaminase-mediated mechanism of adhesion.