Mucosal and disseminated candidiasis in gnotobiotic SCID mice
56
Citation
38
Reference
10
Related Paper
Citation Trend
Abstract:
Mucosal and disseminated candidiasis in gnotobiotic SCID mice Get access E. Balish, E. Balish Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Jensen, J. Jensen Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Warner, T. Warner Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Brekke, J. Brekke Search for other works by this author on: Oxford Academic PubMed Google Scholar B. Leonard B. Leonard Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Medical and Veterinary Mycology, Volume 31, Issue 2, March 1993, Pages 143–154, https://doi.org/10.1080/02681219380000161 Published: 01 March 1993 Article history Accepted: 28 October 1992 Published: 01 March 1993Keywords:
Systemic candidiasis
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.
Antifungal drugs
Cite
Citations (74)
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.
Cite
Citations (4)
AbstrcatTo establish a stable C57BL/6 mouse model of systemic candidiasis, the mice were challenged intravenously via the lateral tail vein with 2 × 107 or 106 C.albicans yeast cells, respectively. And then the organs of mice were taken out to examine the C. albicans and pathology. The results showed that C. albicans could be isolated from the spleen of all the mice and the histologic section of kidney exhibited C. albicans blastospores and hyphae, and abundant inflammatory cells. Mice immunized with phage displayed peptide and heat killed C. albicans acquired a resistance to systemic C. albicans infection as confirmed by fewer C. albicans cells in the kidneys. These results suggest that the C57BL/6 mouse model of systemic candidosis has been established stably when a suitable does of C. albicans was intravenously given to mice. The model may be used for studying the prevention and cure of systemic C. albicans infection.
Systemic candidiasis
Cite
Citations (0)
Abstract Candida albicans is an important human fungal pathogen. Our previous study disclosed that aryloxy‐phenylpiperazine skeleton was a promising molecule to suppress C. albicans virulence by inhibiting hypha formation and biofilm formation. In order to deeply understand the efficacy and mechanism of action of phenylpiperazine compounds, and obtain new derivatives with excellent activity against C. albicans , hence, we synthesized three series of (1‐heteroaryloxy‐2‐hydroxypropyl)‐phenylpiperazines and evaluated their inhibitory activity against C. albicans both in vitro and in vivo in this study. Compared with previously reported aryloxy‐phenylpiperazines, part of these heteroaryloxy derivatives improved their activities by strongly suppressing hypha formation and biofilm formation in C. albicans SC5314. Especially, (9H‐carbazol‐4‐yl)oxy derivatives 25 , 26 , 27 and 28 exhibited strong activity in reducing C. albicans virulence in both human cell lines in vitro and mouse infection models in vivo. The compound 27 attenuated the virulence of various clinical C. albicans strains, including clinical drug‐resistant C. albicans strains. Moreover, additive effects of the compound 27 with antifungal drugs against drug‐resistant C. albicans strains were also discussed. Furthermore, the compound 27 significantly improved the composition and richness of the faecal microbiota in mice infected by C. albicans . These findings indicate that these piperazine compounds have great potential to be developed as new therapeutic drugs against C. albicans infection.
Cite
Citations (3)
Cite
Citations (12)
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.
Virulence factor
Cite
Citations (115)
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.
Immunosuppression
Humoral immunity
Cite
Citations (0)
Objective To develop and identify monoclonal antibodies against germ tubes of Candida albicans(C.albicans).Methods Blastospore of C.albicans ATCC-90028 were used as immunogens to prepare monoclonal antibodies(McABs),which were prepared by the lymphocyte hybridom technique,and were identificated.The result of germ tubes induction,which were induced by NCS,and with the paiticipation of McAb against C.albicans germ tubes,were observed.Results One celling of hybirdomase-creating constantly McAbs against germ tubes of C.albicans,which named McAb03.2C1-C2,was developed.The titer of McAb reached to 1∶25 600;The McAb belonged to IgG1 Lambda isotypes.The result that McAb03.2C1-C2 could specific react to the protein(156kD) antigen of germ tubes of Candida albicans was manifested.IIF diplaid that McAb03.2C1-C2 of mice hydroperitonia could specificly reacted to germ tubes of Candida albicans,but failed to react to phas of spore.Inductive radio of C.albicans germ tubes,which inducted by medium with the addition of McAb against C.albicans germ tube,was lower than inductive radio of C.albicans germ tube inducted by serum.Conclusion It is suggested that McAb03.2C1-C2 could be highly specific McAb against pathtype of Candida albicans-germ tubes,and it might be used in early and quick diagnoses of Systemic of C.albicans with a new prospect.McAb McAb03.2C1-C2,which could inhibited distinctly the diversion of C.albicans,can be a protective factor during the procress of resisting infection of systemic C.albicans.
Germ tube
Cite
Citations (0)
C.albicans. Over an 8-hperiod, plate counts ofC.albicans incubated withalveolar macrophages revealed a decrease incolony-forming units incontrast toC.albicans alone. Inaddition, an assay was developed whichspecifically measured C.albicans [3H]leucine incorporation inthepresenceofalveolar macrophages. Usingthis assay,we observed a 71to93%inhibition ofmacromolecular synthesis inC. albicans whenincubated withalveolar macrophages. Autoradiographic studies showed thattheinhibition ofleucine incorporation was restricted totheingested Candida. Themajorprocess bywhichlarge particles (i.e., >2.5Am)suchasCandidaalbicans and other fungi arecleared fromthelungisprobablythrough themucociliary transport system (4). However, additional clearance mechanisms mustexist forthose large particles whichevade themucociliary action. Thealveolar macrophage (AM)isacandiate forsuchamechanism. Theyhavebeenshown toplaya critical roleintheinactivation of bacteria andclearance ofinert particles (5). In these capacities, theAM aidsinthemaintenanceofanessentially sterile environment in thelungspaces. Todatethere havebeenno reports concerning theinteraction ofC.albicanswiththeAM,although studies withother fungi haveindicated thattheAM hasarather limited roleinprotection ofthehostagainst invasion (2,3). Inthisstudy, we haveinvestigated thein vitro relationship between C.albicans andrabbitAM.Ourdataindicate thattheAM can inhibit thegrowth ofingested C.albicans.
Alveolar macrophage
Cite
Citations (3)
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.
Cite
Citations (0)