THE PROTECTIVE IMMUNE RESPONSE AGAINST VAGINAL CANDIDIASIS: LESSONS LEARNED FROM CLINICAL STUDIES AND ANIMAL MODELS

Recurrent vulvovaginal candidiasis (RVVC) is a significant problem in women of childbearing ages and is caused by Candida albicans, a commensal organism of the intestinal and reproductive tracts. As a result of this commensalism, most healthy individuals have demonstrable Candida -specific adaptive immunity that is considered protective. In women with RVVC, a deficiency/dysfunction of this protective immunity is postulated to affect susceptibility to infection. Although cell-mediated immunity (CMI) is considered important for protection against mucosal candidal infections, little is understood about specific host defenses that are important at the vaginal mucosa. Studies to date suggest that a compartmentalized local, rather than systemic, immunity is important for defense against vaginitis. This review will summarize the current state of knowledge regarding protective host defense mechanisms against vaginal C. albicans infections both from clinical studies and animal models. From these data, hypotheses are presented for what host defense mechanisms appear important for resistance/susceptibility to vaginal infection.     

Candida albicans and candidalysin in inflammatory disorders and cancer

As our understanding of mycology progresses, the impact of fungal microbes on human health has become increasingly evident. Candida albicans is a common commensal fungus that gives rise to local and systemic infections, particularly in immunocompromised patients where it can result in mortality. However, C. albicans has also been quietly linked with a variety of inflammatory disorders, to which it has traditionally been considered incidental; recent studies may now provide new aspects of these relationships for further consideration. This review provides a novel perspective on the impact of C. albicans and its peptide toxin, candidalysin, on human health, exploring their contributions to pathology within a variety of diseases.     

Vulvovaginal candidiasis: Epidemiology,microbiology and risk factors

Abstract

Vulvovaginal candidiasis (VVC) is an infection caused by Candida species that affects millions of women every year. Although Candida albicans is the main cause of VVC, the identification of non-Candida albicans Candida (NCAC) species, especially Candida glabrata, as the cause of this infection, appears to be increasing. The development of VVC is usually attributed to the disturbance of the balance between Candida vaginal colonization and host environment by physiological or nonphysiological changes. Several host-related and behavioral risk factors have been proposed as predisposing factors for VVC. Host-related factors include pregnancy, hormone replacement, uncontrolled diabetes, immunosuppression, antibiotics, glucocorticoids use and genetic predispositions. Behavioral risk factors include use of oral contraceptives, intrauterine device, spermicides and condoms and some habits of hygiene, clothing and sexual practices. Despite a growing list of recognized risk factors, much remains to be elucidated as the role of host versus microorganisms, in inducing VVC and its recurrence. Thus, this review provides information about the current state of knowledge on the risk factors that predispose to VVC, also including a revision of the epidemiology and microbiology of VVC, as well as of Candida virulence factors associated with vaginal pathogenicity.     

The epidemiology,pathogenesis, and diagnosis of vulvovaginal candidosis: A mycological perspective

Vulvovaginal candidosis (VVC) is the second most common cause of vaginitis after bacterial vaginosis, and it is diagnosed in up to 40% of women with vaginal complaints in the primary care setting. Reliable diagnosis of VVC requires a correlation of clinical features with mycological evidence. The mycological methods used for diagnosis include microscopic examination, fungal culture, and antigen tests. Fungal culture can reveal the species of organism(s) responsible for the infection and provide epidemiological data. This report reviews current knowledge about the available diagnostic methods and tests that accurately diagnose VVC, and highlights the importance of fungal culture.     

Lipid Metabolism in Fungi

Abstract

Fungi are widely dispersed in nature and frequently appear as pathogens in the animal and plant kingdoms. The incidence of opportunistic fungal infections in humans has increased due to the human immunodeficiency virus and the application of modern medical approaches that subvert natural protective barriers to infection. Also, fungal blights continue to threaten crops worldwide. As a result, new antifungal agents are needed to address these critical problems. Existing antifungals can be used to effectively treat most cases of topical infection caused by the opportunistic pathogen Candida albicans, which is the principal agent of nosocomially acquired fungal infections. However, life-threatening, disseminated Candida infections are treated with more modest success. Existing antifungals can be toxic or ineffective because of natural resistance or even induced resistance. This limited efficacy largely reflects the restricted range of cellular targets considered during the development of current antifungals. The advancement of highly selective fungicidal reagents requires the recognition of new essential cellular targets. The fungal plasma-membrane proton pump is a high-abundance essential enzyme with a number of well-understood molecular properties that should facilitate the development of new antifungals. The proton pump is important for intracellular pH regulation and the maintenance of electrochemical proton gradients needed for nutrient uptake. It is a member of the P-type class of ion-transport enzymes, which are present in nearly all external cellular membranes. Typical P-type enzymes such as the Na+,K+-ATPase and H+,K+-ATPase are well established as specific targets for surface-active cardiac glycosides and anti-ulcer therapeutics. The development of new classes of selective antifungals targeted to the proton pump will require exploitation of the well-characterized genetic, kinetic, topological, regulatory, and drug-interaction features of the fungal enzyme that discriminate it from related host P-type enzymes. New antifungal drugs of this type should be relevant to the control of fungal pathogens of medical and agricultural importance and may be applicable to the control of intracellular parasites that also depend on closely related proton pumps for survival.     

白色念珠菌感染与口腔癌的关系

口腔癌是头颈部最常见的癌症之一,严重影响患者生存质量和生活水平。白色念珠菌是口腔中最常见的机会性致病真菌,当宿主免疫功能低下时表现出致病性,容易引起念珠菌感染。近年来研究发现白色念珠菌感染与口腔癌关系密切,本文对口腔癌患者白色念珠菌感染的流行病学特点,以及白色念珠菌感染对口腔癌发生发展的影响及其机制研究进行综述。通过回顾相关文献发现:口腔癌患者白色念珠菌感染风险增加,白色念珠菌感染可能通过损伤口腔上皮、产生致癌物质、触发慢性炎症及辅助性T细胞17免疫反应等机制促进口腔癌的发生发展。然而目前这些机制的研究仍比较表浅,缺乏充足的直接证据,未来仍需进行大量研究,以期进一步明确白色念珠菌的促癌机制,为防治口腔癌提供新思路。     

山奈酚对白假丝酵母生物被膜抑制作用的研究

目的 研究山奈酚抗白假丝酵母生物被膜的作用及其可能机制。方法 测定山奈酚对白假丝酵母处于形成过程中的生物被膜和成熟生物被膜代谢活性的影响;测定山奈酚对生物被膜基质产生水平的影响;显微镜下观察山奈酚对菌丝形成的抑制作用;水-烃两相分离法测定山奈酚对白假丝酵母细胞表面疏水性的影响;实时定量RT-PCR法测定山奈酚对生物被膜形成相关基因表达的影响。结果 山奈酚抑制白假丝酵母生物被膜形成,且呈剂量依赖性,同时具有抗成熟生物被膜作用,显著降低生物被膜基质含量;与对照组相比,山奈酚明显抑制白假丝酵母菌丝形成并降低其细胞表面疏水性;经山奈酚处理的白假丝酵母生物被膜形成相关基因BCR1、NRG1和TUP1的表达升高,同时HWP1、EFG1、CPH1、ALS1、ALS3和CSH1的表达下降。结论 山奈酚具有抗白假丝酵母生物被膜活性,其机制与抑制菌丝形成及降低其细胞表面疏水性相关。     

来氟米特对氟康唑体外抗耐药白色念珠菌增效作用研究

目的：研究来氟米特与氟康唑在体外合用对耐药白色念珠菌的抗真菌效果。方法：采用棋盘式微量稀释法测定来氟米特联合氟康唑对15株临床耐药白色念珠菌的最小抑菌浓度MIC₈₀。时间-杀菌曲线验证两药联用对耐药白色念珠菌生长的抑制作用。结果：来氟米特单药对实验所用白色念珠菌均无抗菌活性（MIC₈₀>320μg·mL^-1）。来氟米特联合氟康唑可产生协同抗菌作用,协同指数（FICI）<0.25。用药24h后,时间-杀菌曲线上联合用药组比单用氟康唑组平均降低了3.9log₁₀CFU/mL,证实两药具有协同抑菌作用。结论：来氟米特与氟康唑在体外对耐药白色念珠菌具有良好的协同抗真菌活性。