Copper Nanoparticles Reduce Expression of Key Virulence Genes in Vaginal Candida albicans Infection: Implications for Novel Antifungal Therapies
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In recent decades, the incidence of invasive fungal infections has increased notably. Candida albicans (C. albicans), a common opportunistic fungal pathogen that dwells on human mucosal surfaces, can cause fungal infections, especially in immunocompromised and high-risk surgical patients. In addition, the wide use of antifungal agents has likely contributed to resistance of C. albicans to traditional antifungal drugs, increasing the difficulty of treatment. Thus, it is urgent to identify novel antifungal drugs to cope with C. albicans infections. Heat shock proteins (Hsps) exist in most organisms and are expressed in response to thermal stress. In C. albicans, Hsps control basic physiological activities or virulence via interaction with a variety of diverse regulators of cellular signaling pathways. Moreover, it has been demonstrated that Hsps confer drug resistance to C. albicans. Many studies have shown that disrupting the normal functions of C. albicans Hsps inhibits fungal growth or reverses the tolerance of C. albicans to traditional antifungal drugs. Here, we review known functions of the diverse Hsps family, Hsps-associated intracellular signaling pathways and potential antifungal targets based on these pathways in C. albicans. We hope this review will aid in revealing potential new roles of C. albicans Hsps in addition to canonical heat stress adaptions and provide more insight into identifying potential novel antifungal targets.
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Background: Candida albicans is a special type of yeast that is naturally found on the surface of various mucosal layers of the human body. Biofilms forming is well known synergistic relationship between C. albicans and various organisms with no or little aggressive acted toward each other. Methods and findings: C. albicans that isolated from patient with cutaneous candidiasis was tested for antifungal activity against six species of filamentous fungi by measuring of percentage inhibition. The effects of incubation periods and different concentrations of glucose on the antifungal activity of C. albicans were also tested. The percentage inhibition of growing filamentous fungi had been observed at high values when they cultivated on media that previously cultured with C. albicans than when both of fungi and C. albicans cultured at the same time, especially at low concentrations of glucose. Mucor spp. and C. sitophila had been affected by C. albicans only when they cultivated on media that previously cultured with C. albicans. Conclusion: C. albicans had been shown the ability to inhibit various species of filamentous fungi. Incubation periods and glucose concentrations had been effected on the inhibitory action of C. albicans against other fungi.
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Candida albicans is the most prevalent fungal pathogen of humans, causing a variety of diseases ranging from superficial mucosal infections to deep-seated systemic invasions. Mucus, the gel that coats all wet epithelial surfaces, accommodates C. albicans as part of the normal microbiota, where C. albicans resides asymptomatically in healthy humans. Through a series of in vitro experiments combined with gene expression analysis, we show that mucin biopolymers, the main gel-forming constituents of mucus, induce a new oval-shaped morphology in C. albicans in which a range of genes related to adhesion, filamentation, and biofilm formation are downregulated. We also show that corresponding traits are suppressed, rendering C. albicans impaired in forming biofilms on a range of different synthetic surfaces and human epithelial cells. Our data suggest that mucins can manipulate C. albicans physiology, and we hypothesize that they are key environmental signals for retaining C. albicans in the host-compatible, commensal state.The yeast Candida albicans causes both superficial infections of the mucosa and life-threatening infections upon entering the bloodstream. However, C. albicans is not always harmful and can exist as part of the normal microbiota without causing disease. Internal body surfaces that are susceptible to infection by C. albicans are coated with mucus, which we hypothesize plays an important role in preventing infections. Here, we show that the main components of mucus, mucin glycoproteins, suppress virulence attributes of C. albicans at the levels of gene expression and the corresponding morphological traits. Specifically, mucins suppress attachment to plastic surfaces and human cells, the transition to cell-penetrating hyphae, and the formation of biofilms (drug-resistant microbial communities). Additionally, exposure to mucins induces an elongated morphology that physically resembles the mating-competent opaque state but is phenotypically distinct. We suggest that mucins are potent antivirulence molecules that have therapeutic potential for suppressing C. albicans infections.
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To study the role of anti- C. albicans IgY and serum in protection of C. albicans infection of several animal models. To develop three animal models of C. albicans infection: a burned rat model of C. albicans infection, a mouse model of vaginal candiasis and a immunosuppression mouse model of C. albicans infection. And we compared the contribution of anti- C. albicans IgY and serum to the clearance of the C. albicans in three animal models of C. albicans infection. Anti- C. albicans IgY can protect against C. albicans infection in a burned rat model of C. albicans infection and a mouse model of vaginal candidiasis. The serum can effectively protect the mice from disseminated candidiasis in a immunosuppression mouse model. Humoral immunity component involving anti- C. albicans IgY and serum protect against C. albicans infection in a burned rat model of C. albicans infection ,a mouse model of vaginal candidiasis and a immunosuppression mouse model of C. albicans infection.
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Цель исследования. Изучить факторы риска, клинические симптомы и результаты лечения кандидемии, обусловленной C. albicans и C. non-albicans, у больных с опухолями системы крови. Материалы и методы. В исследование включены больные с опухолями системы крови и кандидемией. Диагноз кандидемии устанавливали на основании выделения Candida spp. из гемокультуры и наличия симптомов инфекции. Результаты и обсуждение. В течение 12 лет (2006-2017) кандидемию диагностировали у 75 больных в возрасте от 17 до 77 лет (медиана 48 лет). Кандидемия обусловлена C. albicans у 34,7% больных, C. non-albicans - у 65,3%. Кандидемия, вызванная C. albicans, преобладала у больных старшей возрастной категории (медиана 56,5 года; р=0,04) и лимфомами (61,5%; р=0.01), с колонизацией слизистой оболочки кишечника тем же видом Candida (88,5%; p=0,002). C. non-albicans чаще выделялась из гемокультуры у больных острыми лейкозами (51%; р=0,01) и у реципиентов аллогенных гемопоэтических клеток (22,5%; р=0,01). Способность к образованию биопленок определялась чаще среди C. non-albicans (59,2%), чем C. albicans (19,2%; p=0,001). Клинические симптомы кандидемии были неспецифичными (температура у 97%). Септический шок развился у 25 (33%) больных с сопоставимой частотой в обеих группах. Диагностика сопутствующих инфекций также сопоставима (73 и 73,5%). Общая выживаемость в течение 30 дней при кандидемии, вызванной C. albicans и C. non-albicans, составила 61,2 и 61,5% Лечение эхинокандином приводило к увеличению выживаемости в сравнении с другими антимикотиками при кандидемии, вызванной как C. albicans (88,9% против 40%; р=0,02), так и C. non-albicans (77,3% против 47,8%). Заключение. Среди возбудителей кандидемий выявлен высокий процент C. non-albicans. В обеих группах наблюдалась высокая летальность. Применение эхинокандинов в качестве стартовой терапии приводило к увеличению выживаемости.
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Since candidiasis is so difficult to eradicate with an antifungal treatment and the existing antimycotics display many limitations, hopefully new sulfone derivatives may overcome these deficiencies. It is pertinent to study new strategies such as sulfone derivatives targeting the virulence attributes of C. albicans that differentiate them from the host. During infections, the pathogenic potential of C. albicans relies on the virulence factors as follows: hydrolytic enzymes, transcriptional factors, adhesion, and development of biofilms. In the article we explored how the above-presented C. albicans fitness and virulence attributes provided a robust response to the environmental stress exerted by sulfones upon C. albicans; C. albicans fitness and virulence attributes are fungal properties whose inactivation attenuates virulence. Our understanding of how these mechanisms and factors are inhibited by sulfones has increased over the last years. As lack of toxicity is a prerequisite for medical approaches, sulfones (non-toxic as assessed in vitro and in vivo) may prove to be useful for reducing C. albicans pathogenesis in humans. The antifungal activity of sulfones dealing with these multiple virulence factors and fitness attributes is discussed.
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In this study, we examined the virulence factors and pathogenesis of Vibrio parahaemolyticus in Epinephelus awoara.The chemotactic motility of V. parahaemolyticus for phagocytosis and intracellular survival in fish macrophages was determined using virulence strains and low-virulence strains of V. parahaemolyticus.We found that the intracellular mean number of virulence strains of V. parahaemolyticus ranged from 0-180 min after co-incubation with macrophages and peripheral leukocytes, was relatively low, and decreased steadily over the observation period.Low-virulence strains of V. parahaemolyticus were unable to survive in peripheral leukocytes and macrophages.Cell viability in response to V. parahaemolyticus was assessed using the MTT assay.Low-virulence V. parahaemolyticus strains exhibited lower cytotoxicity compared to virulent strains.©FUNPEC-RP www.funpecrp.com.
Intracellular parasite
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Candida albicans and Cutibacterium acnes are opportunistic pathogens that co-colonize the human body. They are involved in biofilm-related infections of implanted medical devices. The objective of this study was to evaluate the ability of these species to interact and form polymicrobial biofilms. SEM imaging and adhesion assays showed that C. acnes adhesion to C. albicans did not have a preference for a specific morphological state of C. albicans; bacteria adhered to both hyphal and yeast forms of C. albicans. C. albicans did not influence growth of C. acnes under anaerobic growth conditions, however under aerobic growth condition, C. albicans enhanced early C. acnes biofilm formation. This favorable impact of C. albicans was not mediated by secreted compounds accumulating in the medium, but required the presence of metabolically active C. albicans. The ability of these microorganisms to interact together could modulate the physiopathology of infections.
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