Dear Editor,We report a rare case of endogenous endophthalmitis caused by Candida albicans in a patient with chronic renal failure concomitant hemodialysis.A 71-year-old man with a history of hypertension and 2-year c...Dear Editor,We report a rare case of endogenous endophthalmitis caused by Candida albicans in a patient with chronic renal failure concomitant hemodialysis.A 71-year-old man with a history of hypertension and 2-year chronic renal failure on hemodialysis via a native arteriovenous fistula(AVF)was presented to the local hospital due to fever 3wk ago.No pathogens were detected through blood culture on admission,and his fever gradually subsided with intravenous ceftriaxone sodium.After a week of fever,he experienced progressive blurred vision in both eyes,accompanied by pain and headaches.Subsequent magnetic resonance imaging(MRI)of the brain revealed sinusitis.He had not undergone any previous eye surgeries or trauma.展开更多
Objective:Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms,including coordinated innate and adaptive immune responses,to neutralize invading fungi effectively.Exploring the im...Objective:Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms,including coordinated innate and adaptive immune responses,to neutralize invading fungi effectively.Exploring the immune microenvironment has the potential to inform the development of therapeutic strategies for fungal infections.Methods:The study analyzed individual immune cell profiles in peripheral blood mononuclear cells from Candida albicans-infected mice and healthy control mice using single-cell transcriptomics,fluorescence quantitative PCR,and Western blotting.We investigated intergroup differences in the dynamics of immune cell subpopulation infiltration,pathway enrichment,and differentiation during Candida albicans infection.Results:Our findings indicate that infiltration of CD4^(+)naive cells,regulatory T(Treg)cells,and Microtubules(MT)-associated cells increased after infection,along with impaired T cell activity.Notably,CD4^(+) T cells and plasma cells were enhanced after infection,suggesting that antibody production is dependent on T cells.In addition,we screened 6 hub genes,transcription factor forkhead box protein 3(Foxp3),cytotoxic T-lymphocyte associated protein 4(CTLA4),Interleukin 2 Receptor Subunit Beta(Il2rb),Cd28,C-C Motif Chemokine Ligand 5(Ccl5),and Cd27 for alterations associated with CD4^(+) T cell differentiation.Conclusions:These results provide a comprehensive immunological landscape of the mechanisms of Candida albicans infection and greatly advance our understanding of adaptive immunity in fungal infections.展开更多
Candida albicans PDY-07 was isolated from activated sludge under anaerobic conditions and identified as a member belonging to the genus Candida. Pure culture of C. albicans PDY-07, biodegradation of 4-chlorophenol (4-...Candida albicans PDY-07 was isolated from activated sludge under anaerobic conditions and identified as a member belonging to the genus Candida. Pure culture of C. albicans PDY-07, biodegradation of 4-chlorophenol (4-CP) was carried out under anaerobic conditions in Erlenmeyer flasks at 35°C, with an initial pH of 7.0–7.2 and a starting inoculum of 10%(by volume). The results showed that, under the above-mentioned conditions, C. albicans PDY-07 could thoroughly biodegrade 4-CP up to a concentration of 300mg·L?1 within 244h and that it had a high tolerance potential of up to 440mg·L?1 for 4-CP. With the increase in the initial concentrations of 4-CP, substrate inhibition was obviously enhanced. There was increased consumption of 4-CP, which was not assimilated by the cell for growth but was used to counteract the strong substrate inhibition. In addition, the cell growth and substrate-degradation kinetics of 4-CP as the sole source of carbon and energy for the strain in batch cultures were also investigated over a wide range of substrate concentrations (2.2–350mg·L?1), using the proposed cell growth and degradation kinetic models. The results recorded from these experiments showed that the proposed kinetic models adequately described the dynamic behavior of 4-CP biodegradation by C. albicans PDY-07.展开更多
Objective:To evaluate the antifungal activity of four honeys of different types from Algeria against pathogenic yeast i.e.Candida albicans(C.albicans) and Rhoddtorula sp.Methods:Four Algeria honeys of different botani...Objective:To evaluate the antifungal activity of four honeys of different types from Algeria against pathogenic yeast i.e.Candida albicans(C.albicans) and Rhoddtorula sp.Methods:Four Algeria honeys of different botanical origin were analvzed to test anlilungal effect against C.albicans,and Rhodotorula sp.Different concentrations(undiluted,10%,30%,50%and 70%w/v) of honey were studied in vitro for their antifugal aclivity using C.albicans and Rhodotorula sp.as fungal strains.Results:The range of the c liameter of zone of inhibition of various concentrations ol tested honeys was(7-23 mm) for Rhodotorula sp.,while C.albicans showed clearly resistance towards all concentrations used.The MICs of tested honey concentrations against C.albicans and Rhodotorula sp.were(70.09-93.48)%and(4.90-99.70)%v/v,respectively.Conclusions:This study demonstrales that,in vitro,these natural products have clearly an antifungal activity against Rhodotorula sp.and C.albicans.展开更多
Objective:To evaluate the additive action of ginger starch on the antifungal activity of honey against Candida albicans(C.albicans).Methods:C.albicans was used to determine the minimum inhibitory concentration(MIC)of ...Objective:To evaluate the additive action of ginger starch on the antifungal activity of honey against Candida albicans(C.albicans).Methods:C.albicans was used to determine the minimum inhibitory concentration(MIC)of four varieties of Algerian honey.Lower concentrations of honey than the MIC were incubated with a set of concentrations of starch and then added to media to detennine the minimum additive inhibitory concentration(MAIC).Results:The MIC for the four varieties of honey without starch against C.albicans ranged between 38%and 42%(v/v).When starch was incubated with honey and then added to media,a MIC drop was noticed with each variety.MAIC of the four varieties ranged between 32%honey(v/v)with 4%starch and 36%honey(v/v) with 2%starch.Conclusions:The use of ginger starch allows honey benefit and will constitute an alternative way against the resistance to antifungal agents.展开更多
Objective:To evaluate the antimicrobial activity of ethanolic extract of Ecballium elaterium(E. elaterium)fruits alone against Staphylococcus aureus(S.aureus) strains and Candida albicans(C.albicans)strains,or in comb...Objective:To evaluate the antimicrobial activity of ethanolic extract of Ecballium elaterium(E. elaterium)fruits alone against Staphylococcus aureus(S.aureus) strains and Candida albicans(C.albicans)strains,or in combination with penicillin against Staphylococcus areus strains. Methods:Evaluation of the antimicrobial activity or synergy interaction was carried out using microdilution method.Results:The results showed that ethanolic extract of E.elaterium fruits has antimicrobial activity against methicillin resistant S.aureus(MRSA),methicillin sensitive S. aureus(MSSA) and C.albicans.This extract showed a significant decrease in minimum inhibitory concentrations(MIC)of penicillin against both MRSA and MSSA strains.Fractional inhibitory concentration index(FIC)between penicillin and ethanolic extract of E.elaterium fruits against these test strains was less than 0.5.Conclusions:This study suggests that ethanolic extract of E.elaterium fruits has antimicrobial activity against S.aureus and C.albicans and there is a possibility of concurrent use of penicillin and E.elaterium extract in combination in the treatment of infections caused by MRSA and MSSA strains.A wider study is needed to identify the effective components,the mode of action and the possible toxic effect in vivo of these ingredients.展开更多
Objective:To determine the major changes in the microstructure of Candida albicans(C. albicans) after treatment with Euphorbia hirta(E.hirta) L.leaf extract.Methods:Transmission electron microscopy was used to study t...Objective:To determine the major changes in the microstructure of Candida albicans(C. albicans) after treatment with Euphorbia hirta(E.hirta) L.leaf extract.Methods:Transmission electron microscopy was used to study the ultrastructural changes caused by E.hirta extract on C. albicans cells al various exposure time.Results:It was found that the main abnormalities were the alterations in morphology,lysis and complete collapse of the yeast cells after 36 h of exposure to the extract.Whereas the control cultures showed a typical morphology of Candida with a uniform central density,typically structured nucleus,and a cytoplasm with several elements of endomembrane system and enveloped by a regular,intact cell wall.Conclusions:The significant antifungal activity shown by this methanol extract of E.hirta L.suggests its potential against infections caused by C.albicans.The extract may be developed as an anticandidal agent.展开更多
Objective:To determine the anticandidal activities of Salvia officinalis L.(S.officinalis)essential oil against Candida albicans(C.albicans)and the inhibitory effects on the adhesion of C.albicans to polymethyl methac...Objective:To determine the anticandidal activities of Salvia officinalis L.(S.officinalis)essential oil against Candida albicans(C.albicans)and the inhibitory effects on the adhesion of C.albicans to polymethyl methacrylate(PMMA)resin surface.Methods:Disc diffusion method was first used to test the anticandidal activities of the S.officinalis L.essential oil against the reference strain(ATCC 90028)and 2 clinical strains of C.albicans.Then the minimal inhibitory concentration(MIC)and minimal lethal concentration(MLX)were determined by modified membrane method.The adhesion of C.albicans to PMMA resin surface was assessed after immersion with S.officinalis L.essential oil at various concentrations of 1XMIC.0.5XMIC and 0.25XMIC at room temperature for30 min.One-way ANOVA was used to compare the Candida cell adhesion with the pretreatment agents and Tukey's test was used for multiple comparisons.Results:5.officinalis L.essential oil exhibited anticandidal activity against all strains of C.albicans with inhibition zone ranging from 40.5 mm to 19.5 mm.The MIC and MLC of the oil were determined as 2.780 g/L against all test strains.According to the effects on C.albicans adhesion to PMMA resin surface,it was found that immersion in the essential oil at concentrations of 1XMIC(2.780 g/L).0.5XMIC(1.390 g/L)and0.25XMIC(0.695 g/L)for 30 min significantly reduced the adhesion of all 3 test strains to PMMA resin surface in a dose dependent manner(P<0.05).Conclusions:S.officinalis L.essential oil exhibited anticandidal activities against C.albicans and had inhibitory effects on the adhesion of the cells to PMMA resin surface.With further testing and development,S.officinalis essential oil may be used as an antifungal denture cleanser to prevent candidal adhesion and thus reduce the risk of candida-associated denture stomatitis.展开更多
BACKGROUND:Opportunistic infection of Candida albicans(C.albicans) has become a serious problem in immunocompromised patients.The study aimed to explore the mechanism of enterogenous infection of C.albicans in immunoc...BACKGROUND:Opportunistic infection of Candida albicans(C.albicans) has become a serious problem in immunocompromised patients.The study aimed to explore the mechanism of enterogenous infection of C.albicans in immunocompromised rats under severe acute pancreatitis(SAP).METHODS:Sprague Dawley(SD) rats(n=100) were randomly assigned into 5 groups as the following:blank group,cyclophosphamide+ceftriaxone+SAP group,cyclophosphamide+ceftriaxone group,cyclophosphamide+SAP group,and cyclophosphamide group.The rats were sacrificed at 5and 10 days,and their jejunum,colon,mesenteric lymph nodes,pancreas,intestinal content,and blood were quickly collected to detect C.albicans.A region of the 25 S rRNA gene was chosen and amplified by polymerase chain reaction(PCR) to differentiate C.albicans genotypes.The amplified products were further sequenced and compared to judge their homology.RESULTS:Compared with the Cyclophosphamide group,the combination of immunosuppressants and broad-spectrum antibiotics significantly increased the colonization of C.albicans in intestine in 5 and 10 days.Pure SAP stress did not increase the opportunistic infection of C.albicans.The PCR products of C.albicans isolates all belonged to the genotype A family,and sequence alignment showed that the amplified fragments were homologous.CONCLUSION:The damage of immune system and broad-spectrum antimicrobial agents are important risk factors for opportunistic fungal infection.Intestinal tract is an important source for genotype-A C.albicans to translocate and invade into bloodstream.展开更多
Objective:To detect the anticandidal activity of nine toothpastes containing sodium fluoride, sodium monofluorophosphate and herbal extracts as an active ingredients against 45 oral and non oral Candida albicans(C.alb...Objective:To detect the anticandidal activity of nine toothpastes containing sodium fluoride, sodium monofluorophosphate and herbal extracts as an active ingredients against 45 oral and non oral Candida albicans(C.albicans) isolates.Methods:The antifungal activity of these toothpaste formulations was determined using a standard agar well diffusion method.Statistical analysis was performed using a statistical package,SPSS windows version 15,by applying mean values using one-way ANOVA with post-hoc least square differences(LSD) method.A P value of less than 0.05 was considered significant.Results:All toothpastes studied in our experiments were effective in inhibiting the growth of all C.albicans isolates.The highest anticandidal activity was obtained from toothpaste that containing both herbal extracts and sodium fluoride as active ingredients, while the lowest activity was obtained from toothpaste containing sodium monofluorophosphate as an active ingredient.Antifungal activity of Parodontax toothpaste showed a significant difference(P<0.001) against C.albicans isolates compared to toothpastes containing sodium fluoride or herbal products.Conclusions:In the present study,it has been demonstrated that toothpaste containing both herbal extracts and sodium fluoride as active ingredients are more effective in control of C.albicans,while toothpaste that containing monofluorophosphate as an active ingredient is less effective against C.albicans.Some herbal toothpaste formulations studied in our experiments,appear to be equally effective as the fluoride dental formulations and it can be used as an alternative to conventional formulations for individuals who have an interest in naturally-based products.Our results may provide invaluable information for dental professionals.展开更多
AIMTo determine the association between chlamydial conjunctivitis and genital infection by Chlamydia trachomatis, Mycoplasma genitalium and Candida albicans, in addition to the possible relationship between cultured b...AIMTo determine the association between chlamydial conjunctivitis and genital infection by Chlamydia trachomatis, Mycoplasma genitalium and Candida albicans, in addition to the possible relationship between cultured bacterial pathogens and oculogenital chlamydial infection.METHODSThis study was performed on 100 (50 symptomatic and 50 asymptomatic) women attending the Gynecological and Obstetric outpatient clinic of Alzahra hospital, Alazhar University. Simultaneously a conjunctival swab was taken from these patients. Polymerase chain reaction (PCR) was done on DNA extracted from both vaginal and conjunctival swab samples. Culture for both vaginal and conjunctival swabs was also done.RESULTSCandida albicans was the predominant organism isolated by culture in 20% and 40% of conjunctival and vaginal swabs respectively. By the PCR method, ocular Chlamydia trachomatis was present in 60% of symptomatic women, while genital Chlamydia trachomatis infection was present in 30% of symptomatic women. The results of this method also indicated that 25/50 (50%) vaginal swabs were positive with PCR for Candida albicans versus 15/50 (30%) were PCR positive in conjunctival swab. Mycoplasma genitalium was present in only 10% of vaginal swabs. Concomitant oculogenital PCR positive results for Chlamydia trachomatis and Candida albicans were 30% and 28% respectively.CONCLUSIONOcular Chlamydia trachomatis was associated with genital Chlamydia trachomatis in a high percentage of women followed by Candida albicans. Cultured bacterial organisms do not play a role in enhancement of Chlamydia trachomatis infection.展开更多
Objective:To analyze the antifungal effects of Chinese herb monomers,i.e.berberine,baicalin,eugenol and curcumin,on Candida albicans.Methods:After Candida albicans strain Y01-09 was incubated for 48 h in YEPD broth wh...Objective:To analyze the antifungal effects of Chinese herb monomers,i.e.berberine,baicalin,eugenol and curcumin,on Candida albicans.Methods:After Candida albicans strain Y01-09 was incubated for 48 h in YEPD broth which contained different concentrations of Chinese herb components,the cell cycle,fluorescent intensity and the size of cell volume were detected by flow cytometry.Results:The 4 Chinese herb monomers could affect the cell cycle of Candida albicans in different ranges.The ratio of cells in S-G2-M period decreased as the agents concentration increased,indicating that the cell division was inhibited.The fluorescent intensity of Candida albicans cells became weaker after being incubated,which reflected the loss of DNA fragments.The higher the concentration was,the weaker the fluorescent intensity became.The cell size,cell diopter and particle size changed much as the agents concentration increased.Conclusion:Chinese herb monomers play the antifungal role in inhibiting cell division.FCM could be used to determine the susceptibility of antifungal agents.展开更多
Candida albicans PDY-07 was isolated from activated sludge under anaerobic conditions and identified as a member belonging to the genus Candida. Pure culture of C. albicans PDY-07, biodegradation of 4-chlorophenol 4-C...Candida albicans PDY-07 was isolated from activated sludge under anaerobic conditions and identified as a member belonging to the genus Candida. Pure culture of C. albicans PDY-07, biodegradation of 4-chlorophenol 4-CP was carried out under anaerobic conditions in Erlenmeyer flasks at 35℃, with an initial pH of 7.0—7.2 and a starting inoculum of 10% by volume. The results showed that, under the above-mentioned con- ditions, C. albicans PDY-07 could thoroughly biodegrade 4-CP up to a concentration of 300mg·L-1 within 244h and that it had a high tolerance potential of up to 440mg·L-1 for 4-CP. With the increase in the initial concentrations of 4-CP, substrate inhibition was obviously enhanced. There was increased consumption of 4-CP, which was not assimilated by the cell for growth but was used to counteract the strong substrate inhibition. In addition, the cell growth and substrate-degradation kinetics of 4-CP as the sole source of carbon and energy for the strain in batch cultures were also investigated over a wide range of substrate concentrations 2.2—350mg·L-1, using the proposed cell growth and degradation kinetic models. The results recorded from these experiments showed that the proposed kinetic models adequately described the dynamic behavior of 4-CP biodegradation by C. albicans PDY-07.展开更多
Aim To identify heterogeneity of Candida albicans (C. albicans) isolated from the population with cancer in China by using identification medium, subculture molecular typing, and antifungal susceptibility test. Meth...Aim To identify heterogeneity of Candida albicans (C. albicans) isolated from the population with cancer in China by using identification medium, subculture molecular typing, and antifungal susceptibility test. Methodology Oral cheek mucosal specimens from 52 cancer patients receiving chemotherapy were cultured on CHROMagar CandidaTM plates for Candida identification. All the C. albicans colonies on the plates were subcultured and reconfirmed by API20C, then submitted to the antifimgal drug susceptibility test with fluconazole and molecular typing using randomly amplified polymorphic DNA-PCR (RAPD) with primers RSD6 and RSD12.Results 54% (28/52) patients were oral yeast carriage in which C. albicans predominated. More than 7 C. albicans colonies were isolated from each of 12 patients (Group A), while less than 5 colonies were isolated from each of 16 patients (Group B). RSD6 and RSD12 were successful in eliciting 17 (A1-A17) and 2 (B1-B2) genotypes, respectively from among the 205 isolates. The two primers were combined to generate 21 genotypes. The C. albicans isolates obtained from the same patient and episode showed a diversity for fluconazole revealed by MIC50 and MIC90. Conclusion The heterogeneity of the C. albicans colonies isolated from the same patients can be detected. C. albicans with varied fluconazole susceptibility and genotypic characteristics may coexist in the same oral Candida population.展开更多
More studies have indicated that polysaccharide sulfate has anti-coagulant activity.Now,heparin is the most popular anticoagulant used in clinic,however,its side effects have also caused highly concern.It is still und...More studies have indicated that polysaccharide sulfate has anti-coagulant activity.Now,heparin is the most popular anticoagulant used in clinic,however,its side effects have also caused highly concern.It is still under intensive investigations to synthesize effective safe polysaccharide sulfate as heparin substitute.We extracted water-soluble polysaccharide from fermented mycelium of edible polyporus albicans(Imaz.) teng,and got the water-soluble polyporus albicans teng sulfate(PATS) by modifying the water-solubility polyose with the method of chlorosulfonic acid-pyridine.The anti-coagulant assay of PATS in vitro towards normal human plasma indicates its remarkable anticoagulant activity,while the dose could be as low as 5 mg/L for anticoagulation.The anti-coagulant effect was equivalent to that of heparin about 150 U when the concentration of PATS was 10 mg/L.The study on anti-coagulation mechanism suggests that PATS got involved in the intrinsic pathway.The anti-coagulation activity of PATS was due to the inhibition of the coagulation factors IIa and Xa activities mediated by antithrombin Ⅲ(ATIII).The anti-coagulation mechanism of PATS is absolutely identical to that of heparin.In conclusion,we suggest that PATS has the similar anti-coagulation characteristic to heparin,but with a better anti-coagulation effect.Meanwhile,derived from edible fungus-polysaccharide,PATS has more bio-safety advantage.Therefore,PATS has promising future to be developed and used as an ideal substitute for heparin in clinic.展开更多
The model of vaginal candidiasis in Kunming mice was constructed in order to search for the optima construction conditions and provide an economic animal model of Candida albicans (C. albicans) vaginitis. Estrogen ben...The model of vaginal candidiasis in Kunming mice was constructed in order to search for the optima construction conditions and provide an economic animal model of Candida albicans (C. albicans) vaginitis. Estrogen benzoate (E2) was given to mice at different concentrations ranging from 0.0 to 0.05 mg/mouse (4 levels) beginning 72 h prior to vaginal inoculation, then mice were in- oculated intravaginally with various concentrations of stationary-phase C. albicans blastoconidia (ATCC90028) (5 levels) in 20 μL of phosphate-buffered saline (PBS) in each E2 level. General state, scores of genital pathology, the hyphae and vaginal fungal burden (CFU) in vaginal lavage fluid, the hydrops rate of uterus and vaginal tissues for pathological section in mice were observed and ob- tained at day 2, 4, 7, 14 and 21 after inoculation. The results showed the infection rate in mice was related to the dosage of E2 and concentration of C. albicans blastoconidia. Additionally there was better cross-effect between the two treated factors. The infection rate was about 80% on the day 4, and could reach 100% on the day 7 until the end of experiment after inoculated intravaginally in groups of E2I3, E2 0.025 mg/mouse injected hypodermically and inoculated intravaginally with 5×104 C. albicans blastoconidia, and large amount of hyphae and blastoconidia could be observe in superfi- cial layer tissue and canal of vaginal by PAS. From the results in our experiment it was concluded that E2I3 was the optima construction condition in kunming mice.展开更多
To compare the therapeutic effects of three different anti-fungal drugs (i.e., terbinafine, fluconazole and intraconazole) in the treatment of experimental vaginitis caused by Candida albicans (C. albicans) in mic...To compare the therapeutic effects of three different anti-fungal drugs (i.e., terbinafine, fluconazole and intraconazole) in the treatment of experimental vaginitis caused by Candida albicans (C. albicans) in mice, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans after the animal had been pretreated with estradiol. Mice were divided at random into different groups and then respectively treated with terbinafine, fluconazole and intraconazole given by gastrogavage. The burden of the fungus in the vaginal lavage fluids in the mice of the different groups was measured dynamically at different time points after the beginning of the drug treatment. The fungal burdens in the vaginal lavage fluids taken at different time points from the mice treated with terbinafine were significantly higher than those taken at corresponding time points from mice treated with fluconazole or itraconazole (P〈0.01). The fungal burdens in the vaginal lavage fluids taken from mice 1 week after the beginning of the treatment with terbinafine remained at a relatively high level. A dramatic drop in the fungal burden was noted in the vaginal lavage fluids taken on the 2nd day of the treatment from mice treated with itraconazole or fluconazole group and the fungal burden on the 3rd day of the treatment in these mice were at a very low level, suggesting that fluconazole or itraconazole were highly effective for the treatment. However, the difference in the therapeutic effect between the two drugs was not significant (P〉0.05). Itraconazole or fluconazole, but not terbinafine, is very effective for the treatment of fungal vaginitis caused by C. albicans in mice.展开更多
Objective To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid(BDSF) and fluconazole(FLU) or itraconazole(ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in...Objective To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid(BDSF) and fluconazole(FLU) or itraconazole(ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo. Methods Minimum inhibitory concentrations(MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction(qR T-PCR). Results BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ≤ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qR T-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mR NA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis. Conclusion The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.展开更多
Cells of Candida albicans(C.albicans) can invade humans and may lead to mucosal and skin infections or to deep-seated my coses of almost all inner organs,especially in immunocompromised patients.In this context,both t...Cells of Candida albicans(C.albicans) can invade humans and may lead to mucosal and skin infections or to deep-seated my coses of almost all inner organs,especially in immunocompromised patients.In this context,both the host immune status and the ability of C.albicans to modulate the expression of its virulence factors are relevant aspects that drive the candidal susceptibility or resistance;in this last case,culminating in the establishment of successful infection knownas candidiasis.C.albicans possesses a potent arma-mentarium consisting of several virulence moleculesthat help the fungal cells to escape of the host immuneresponses.There is no doubt that the secretion of aspartyl-type proteases,designated as Saps,are one of the major virulence attributes produced by C.albicans cells,since these hydrolytic enzymes participate in a wide range of fungal physiological processes as well as in different facets of the fungal-host interactions.For these reasons,Saps clearly hold promise as new potential drug targets.Corroborating this hypothesis,the introduction of new anti-human immunodeficiency virus drugs of the as party l protease inhibitor-type(HIV PIs) have emerged as new agents for the inhibition of Saps.The introduction of HIV PIs has revolutionized the treatment of HIV disease,reducing opportunistic infections,especially candidiasis.The attenuation of candidal infections in HIV-infected individuals might not solely have resulted from improved immunological status,but also as a result of direct inhibition of C.albicans Saps.In this article,we review updates on the beneficial effects of HIV PIs against the human fungal pathogen C.albicans,focusing on the effects of these compounds on Sap activity,growth behavior,morphological architecture,cellular differentiation,fungal adhesion to animal cells and abiotic materials,modulation of virulence factors,experimental candidiasis infection,and their synergistic actions with classical antifungal agents.展开更多
基金the National Natural Science Foundation of China(No.82171072)the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515010921).
文摘Dear Editor,We report a rare case of endogenous endophthalmitis caused by Candida albicans in a patient with chronic renal failure concomitant hemodialysis.A 71-year-old man with a history of hypertension and 2-year chronic renal failure on hemodialysis via a native arteriovenous fistula(AVF)was presented to the local hospital due to fever 3wk ago.No pathogens were detected through blood culture on admission,and his fever gradually subsided with intravenous ceftriaxone sodium.After a week of fever,he experienced progressive blurred vision in both eyes,accompanied by pain and headaches.Subsequent magnetic resonance imaging(MRI)of the brain revealed sinusitis.He had not undergone any previous eye surgeries or trauma.
基金supported by National Key Research and Development Program of China(2021YFC2301405)Chongqing Talent Program(No.CQYC202003220).
文摘Objective:Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms,including coordinated innate and adaptive immune responses,to neutralize invading fungi effectively.Exploring the immune microenvironment has the potential to inform the development of therapeutic strategies for fungal infections.Methods:The study analyzed individual immune cell profiles in peripheral blood mononuclear cells from Candida albicans-infected mice and healthy control mice using single-cell transcriptomics,fluorescence quantitative PCR,and Western blotting.We investigated intergroup differences in the dynamics of immune cell subpopulation infiltration,pathway enrichment,and differentiation during Candida albicans infection.Results:Our findings indicate that infiltration of CD4^(+)naive cells,regulatory T(Treg)cells,and Microtubules(MT)-associated cells increased after infection,along with impaired T cell activity.Notably,CD4^(+) T cells and plasma cells were enhanced after infection,suggesting that antibody production is dependent on T cells.In addition,we screened 6 hub genes,transcription factor forkhead box protein 3(Foxp3),cytotoxic T-lymphocyte associated protein 4(CTLA4),Interleukin 2 Receptor Subunit Beta(Il2rb),Cd28,C-C Motif Chemokine Ligand 5(Ccl5),and Cd27 for alterations associated with CD4^(+) T cell differentiation.Conclusions:These results provide a comprehensive immunological landscape of the mechanisms of Candida albicans infection and greatly advance our understanding of adaptive immunity in fungal infections.
基金Supported by the National Natural Science Foundation of China (No.20336030) and the Natural Science Foundation of Tianjin(No.05YFJZJC 00500).
文摘Candida albicans PDY-07 was isolated from activated sludge under anaerobic conditions and identified as a member belonging to the genus Candida. Pure culture of C. albicans PDY-07, biodegradation of 4-chlorophenol (4-CP) was carried out under anaerobic conditions in Erlenmeyer flasks at 35°C, with an initial pH of 7.0–7.2 and a starting inoculum of 10%(by volume). The results showed that, under the above-mentioned conditions, C. albicans PDY-07 could thoroughly biodegrade 4-CP up to a concentration of 300mg·L?1 within 244h and that it had a high tolerance potential of up to 440mg·L?1 for 4-CP. With the increase in the initial concentrations of 4-CP, substrate inhibition was obviously enhanced. There was increased consumption of 4-CP, which was not assimilated by the cell for growth but was used to counteract the strong substrate inhibition. In addition, the cell growth and substrate-degradation kinetics of 4-CP as the sole source of carbon and energy for the strain in batch cultures were also investigated over a wide range of substrate concentrations (2.2–350mg·L?1), using the proposed cell growth and degradation kinetic models. The results recorded from these experiments showed that the proposed kinetic models adequately described the dynamic behavior of 4-CP biodegradation by C. albicans PDY-07.
基金supported by project CNEPRU,Institute of Veterinary Sciences(IVS),University Ibn-Khaldoun(TIARET),Algeria(grant No.F023 2009/0009)
文摘Objective:To evaluate the antifungal activity of four honeys of different types from Algeria against pathogenic yeast i.e.Candida albicans(C.albicans) and Rhoddtorula sp.Methods:Four Algeria honeys of different botanical origin were analvzed to test anlilungal effect against C.albicans,and Rhodotorula sp.Different concentrations(undiluted,10%,30%,50%and 70%w/v) of honey were studied in vitro for their antifugal aclivity using C.albicans and Rhodotorula sp.as fungal strains.Results:The range of the c liameter of zone of inhibition of various concentrations ol tested honeys was(7-23 mm) for Rhodotorula sp.,while C.albicans showed clearly resistance towards all concentrations used.The MICs of tested honey concentrations against C.albicans and Rhodotorula sp.were(70.09-93.48)%and(4.90-99.70)%v/v,respectively.Conclusions:This study demonstrales that,in vitro,these natural products have clearly an antifungal activity against Rhodotorula sp.and C.albicans.
基金financially supported by project CNEPRU,Institute of Veterinary Sciences.University Ibn-Khaldoun(TIARET).Algeria(grant No.F0232009/0009)
文摘Objective:To evaluate the additive action of ginger starch on the antifungal activity of honey against Candida albicans(C.albicans).Methods:C.albicans was used to determine the minimum inhibitory concentration(MIC)of four varieties of Algerian honey.Lower concentrations of honey than the MIC were incubated with a set of concentrations of starch and then added to media to detennine the minimum additive inhibitory concentration(MAIC).Results:The MIC for the four varieties of honey without starch against C.albicans ranged between 38%and 42%(v/v).When starch was incubated with honey and then added to media,a MIC drop was noticed with each variety.MAIC of the four varieties ranged between 32%honey(v/v)with 4%starch and 36%honey(v/v) with 2%starch.Conclusions:The use of ginger starch allows honey benefit and will constitute an alternative way against the resistance to antifungal agents.
文摘Objective:To evaluate the antimicrobial activity of ethanolic extract of Ecballium elaterium(E. elaterium)fruits alone against Staphylococcus aureus(S.aureus) strains and Candida albicans(C.albicans)strains,or in combination with penicillin against Staphylococcus areus strains. Methods:Evaluation of the antimicrobial activity or synergy interaction was carried out using microdilution method.Results:The results showed that ethanolic extract of E.elaterium fruits has antimicrobial activity against methicillin resistant S.aureus(MRSA),methicillin sensitive S. aureus(MSSA) and C.albicans.This extract showed a significant decrease in minimum inhibitory concentrations(MIC)of penicillin against both MRSA and MSSA strains.Fractional inhibitory concentration index(FIC)between penicillin and ethanolic extract of E.elaterium fruits against these test strains was less than 0.5.Conclusions:This study suggests that ethanolic extract of E.elaterium fruits has antimicrobial activity against S.aureus and C.albicans and there is a possibility of concurrent use of penicillin and E.elaterium extract in combination in the treatment of infections caused by MRSA and MSSA strains.A wider study is needed to identify the effective components,the mode of action and the possible toxic effect in vivo of these ingredients.
文摘Objective:To determine the major changes in the microstructure of Candida albicans(C. albicans) after treatment with Euphorbia hirta(E.hirta) L.leaf extract.Methods:Transmission electron microscopy was used to study the ultrastructural changes caused by E.hirta extract on C. albicans cells al various exposure time.Results:It was found that the main abnormalities were the alterations in morphology,lysis and complete collapse of the yeast cells after 36 h of exposure to the extract.Whereas the control cultures showed a typical morphology of Candida with a uniform central density,typically structured nucleus,and a cytoplasm with several elements of endomembrane system and enveloped by a regular,intact cell wall.Conclusions:The significant antifungal activity shown by this methanol extract of E.hirta L.suggests its potential against infections caused by C.albicans.The extract may be developed as an anticandidal agent.
基金Supported by Maxillofacial Prosthetic Service Research Fund,Faculty of Dentistry,Mahidol University,Bangkok,Thailand(Grant No.496/2011)
文摘Objective:To determine the anticandidal activities of Salvia officinalis L.(S.officinalis)essential oil against Candida albicans(C.albicans)and the inhibitory effects on the adhesion of C.albicans to polymethyl methacrylate(PMMA)resin surface.Methods:Disc diffusion method was first used to test the anticandidal activities of the S.officinalis L.essential oil against the reference strain(ATCC 90028)and 2 clinical strains of C.albicans.Then the minimal inhibitory concentration(MIC)and minimal lethal concentration(MLX)were determined by modified membrane method.The adhesion of C.albicans to PMMA resin surface was assessed after immersion with S.officinalis L.essential oil at various concentrations of 1XMIC.0.5XMIC and 0.25XMIC at room temperature for30 min.One-way ANOVA was used to compare the Candida cell adhesion with the pretreatment agents and Tukey's test was used for multiple comparisons.Results:5.officinalis L.essential oil exhibited anticandidal activity against all strains of C.albicans with inhibition zone ranging from 40.5 mm to 19.5 mm.The MIC and MLC of the oil were determined as 2.780 g/L against all test strains.According to the effects on C.albicans adhesion to PMMA resin surface,it was found that immersion in the essential oil at concentrations of 1XMIC(2.780 g/L).0.5XMIC(1.390 g/L)and0.25XMIC(0.695 g/L)for 30 min significantly reduced the adhesion of all 3 test strains to PMMA resin surface in a dose dependent manner(P<0.05).Conclusions:S.officinalis L.essential oil exhibited anticandidal activities against C.albicans and had inhibitory effects on the adhesion of the cells to PMMA resin surface.With further testing and development,S.officinalis essential oil may be used as an antifungal denture cleanser to prevent candidal adhesion and thus reduce the risk of candida-associated denture stomatitis.
基金supported by grants from the Research Foundation of Shanghai Minhang District Municipal Commission of Health and Family Planning(2013MW12)the Research Foundation of Shanghai Municipal Commission of Health and Family Planning(201540136)
文摘BACKGROUND:Opportunistic infection of Candida albicans(C.albicans) has become a serious problem in immunocompromised patients.The study aimed to explore the mechanism of enterogenous infection of C.albicans in immunocompromised rats under severe acute pancreatitis(SAP).METHODS:Sprague Dawley(SD) rats(n=100) were randomly assigned into 5 groups as the following:blank group,cyclophosphamide+ceftriaxone+SAP group,cyclophosphamide+ceftriaxone group,cyclophosphamide+SAP group,and cyclophosphamide group.The rats were sacrificed at 5and 10 days,and their jejunum,colon,mesenteric lymph nodes,pancreas,intestinal content,and blood were quickly collected to detect C.albicans.A region of the 25 S rRNA gene was chosen and amplified by polymerase chain reaction(PCR) to differentiate C.albicans genotypes.The amplified products were further sequenced and compared to judge their homology.RESULTS:Compared with the Cyclophosphamide group,the combination of immunosuppressants and broad-spectrum antibiotics significantly increased the colonization of C.albicans in intestine in 5 and 10 days.Pure SAP stress did not increase the opportunistic infection of C.albicans.The PCR products of C.albicans isolates all belonged to the genotype A family,and sequence alignment showed that the amplified fragments were homologous.CONCLUSION:The damage of immune system and broad-spectrum antimicrobial agents are important risk factors for opportunistic fungal infection.Intestinal tract is an important source for genotype-A C.albicans to translocate and invade into bloodstream.
基金Supported by the Deanship of Scientific Research of Najah N.University
文摘Objective:To detect the anticandidal activity of nine toothpastes containing sodium fluoride, sodium monofluorophosphate and herbal extracts as an active ingredients against 45 oral and non oral Candida albicans(C.albicans) isolates.Methods:The antifungal activity of these toothpaste formulations was determined using a standard agar well diffusion method.Statistical analysis was performed using a statistical package,SPSS windows version 15,by applying mean values using one-way ANOVA with post-hoc least square differences(LSD) method.A P value of less than 0.05 was considered significant.Results:All toothpastes studied in our experiments were effective in inhibiting the growth of all C.albicans isolates.The highest anticandidal activity was obtained from toothpaste that containing both herbal extracts and sodium fluoride as active ingredients, while the lowest activity was obtained from toothpaste containing sodium monofluorophosphate as an active ingredient.Antifungal activity of Parodontax toothpaste showed a significant difference(P<0.001) against C.albicans isolates compared to toothpastes containing sodium fluoride or herbal products.Conclusions:In the present study,it has been demonstrated that toothpaste containing both herbal extracts and sodium fluoride as active ingredients are more effective in control of C.albicans,while toothpaste that containing monofluorophosphate as an active ingredient is less effective against C.albicans.Some herbal toothpaste formulations studied in our experiments,appear to be equally effective as the fluoride dental formulations and it can be used as an alternative to conventional formulations for individuals who have an interest in naturally-based products.Our results may provide invaluable information for dental professionals.
文摘AIMTo determine the association between chlamydial conjunctivitis and genital infection by Chlamydia trachomatis, Mycoplasma genitalium and Candida albicans, in addition to the possible relationship between cultured bacterial pathogens and oculogenital chlamydial infection.METHODSThis study was performed on 100 (50 symptomatic and 50 asymptomatic) women attending the Gynecological and Obstetric outpatient clinic of Alzahra hospital, Alazhar University. Simultaneously a conjunctival swab was taken from these patients. Polymerase chain reaction (PCR) was done on DNA extracted from both vaginal and conjunctival swab samples. Culture for both vaginal and conjunctival swabs was also done.RESULTSCandida albicans was the predominant organism isolated by culture in 20% and 40% of conjunctival and vaginal swabs respectively. By the PCR method, ocular Chlamydia trachomatis was present in 60% of symptomatic women, while genital Chlamydia trachomatis infection was present in 30% of symptomatic women. The results of this method also indicated that 25/50 (50%) vaginal swabs were positive with PCR for Candida albicans versus 15/50 (30%) were PCR positive in conjunctival swab. Mycoplasma genitalium was present in only 10% of vaginal swabs. Concomitant oculogenital PCR positive results for Chlamydia trachomatis and Candida albicans were 30% and 28% respectively.CONCLUSIONOcular Chlamydia trachomatis was associated with genital Chlamydia trachomatis in a high percentage of women followed by Candida albicans. Cultured bacterial organisms do not play a role in enhancement of Chlamydia trachomatis infection.
文摘Objective:To analyze the antifungal effects of Chinese herb monomers,i.e.berberine,baicalin,eugenol and curcumin,on Candida albicans.Methods:After Candida albicans strain Y01-09 was incubated for 48 h in YEPD broth which contained different concentrations of Chinese herb components,the cell cycle,fluorescent intensity and the size of cell volume were detected by flow cytometry.Results:The 4 Chinese herb monomers could affect the cell cycle of Candida albicans in different ranges.The ratio of cells in S-G2-M period decreased as the agents concentration increased,indicating that the cell division was inhibited.The fluorescent intensity of Candida albicans cells became weaker after being incubated,which reflected the loss of DNA fragments.The higher the concentration was,the weaker the fluorescent intensity became.The cell size,cell diopter and particle size changed much as the agents concentration increased.Conclusion:Chinese herb monomers play the antifungal role in inhibiting cell division.FCM could be used to determine the susceptibility of antifungal agents.
基金the National Natural Science Foundation of China (No.20336030) the Natural Science Foundation of Tianjin(No.05YFJZJC 00500)
文摘Candida albicans PDY-07 was isolated from activated sludge under anaerobic conditions and identified as a member belonging to the genus Candida. Pure culture of C. albicans PDY-07, biodegradation of 4-chlorophenol 4-CP was carried out under anaerobic conditions in Erlenmeyer flasks at 35℃, with an initial pH of 7.0—7.2 and a starting inoculum of 10% by volume. The results showed that, under the above-mentioned con- ditions, C. albicans PDY-07 could thoroughly biodegrade 4-CP up to a concentration of 300mg·L-1 within 244h and that it had a high tolerance potential of up to 440mg·L-1 for 4-CP. With the increase in the initial concentrations of 4-CP, substrate inhibition was obviously enhanced. There was increased consumption of 4-CP, which was not assimilated by the cell for growth but was used to counteract the strong substrate inhibition. In addition, the cell growth and substrate-degradation kinetics of 4-CP as the sole source of carbon and energy for the strain in batch cultures were also investigated over a wide range of substrate concentrations 2.2—350mg·L-1, using the proposed cell growth and degradation kinetic models. The results recorded from these experiments showed that the proposed kinetic models adequately described the dynamic behavior of 4-CP biodegradation by C. albicans PDY-07.
基金supported by grants from the National Nature Science Foundation of China (No. 30400498)
文摘Aim To identify heterogeneity of Candida albicans (C. albicans) isolated from the population with cancer in China by using identification medium, subculture molecular typing, and antifungal susceptibility test. Methodology Oral cheek mucosal specimens from 52 cancer patients receiving chemotherapy were cultured on CHROMagar CandidaTM plates for Candida identification. All the C. albicans colonies on the plates were subcultured and reconfirmed by API20C, then submitted to the antifimgal drug susceptibility test with fluconazole and molecular typing using randomly amplified polymorphic DNA-PCR (RAPD) with primers RSD6 and RSD12.Results 54% (28/52) patients were oral yeast carriage in which C. albicans predominated. More than 7 C. albicans colonies were isolated from each of 12 patients (Group A), while less than 5 colonies were isolated from each of 16 patients (Group B). RSD6 and RSD12 were successful in eliciting 17 (A1-A17) and 2 (B1-B2) genotypes, respectively from among the 205 isolates. The two primers were combined to generate 21 genotypes. The C. albicans isolates obtained from the same patient and episode showed a diversity for fluconazole revealed by MIC50 and MIC90. Conclusion The heterogeneity of the C. albicans colonies isolated from the same patients can be detected. C. albicans with varied fluconazole susceptibility and genotypic characteristics may coexist in the same oral Candida population.
文摘More studies have indicated that polysaccharide sulfate has anti-coagulant activity.Now,heparin is the most popular anticoagulant used in clinic,however,its side effects have also caused highly concern.It is still under intensive investigations to synthesize effective safe polysaccharide sulfate as heparin substitute.We extracted water-soluble polysaccharide from fermented mycelium of edible polyporus albicans(Imaz.) teng,and got the water-soluble polyporus albicans teng sulfate(PATS) by modifying the water-solubility polyose with the method of chlorosulfonic acid-pyridine.The anti-coagulant assay of PATS in vitro towards normal human plasma indicates its remarkable anticoagulant activity,while the dose could be as low as 5 mg/L for anticoagulation.The anti-coagulant effect was equivalent to that of heparin about 150 U when the concentration of PATS was 10 mg/L.The study on anti-coagulation mechanism suggests that PATS got involved in the intrinsic pathway.The anti-coagulation activity of PATS was due to the inhibition of the coagulation factors IIa and Xa activities mediated by antithrombin Ⅲ(ATIII).The anti-coagulation mechanism of PATS is absolutely identical to that of heparin.In conclusion,we suggest that PATS has the similar anti-coagulation characteristic to heparin,but with a better anti-coagulation effect.Meanwhile,derived from edible fungus-polysaccharide,PATS has more bio-safety advantage.Therefore,PATS has promising future to be developed and used as an ideal substitute for heparin in clinic.
基金the National "10th Five-Year"Key Technologies R&D (No.2004BA709B13-02)
文摘The model of vaginal candidiasis in Kunming mice was constructed in order to search for the optima construction conditions and provide an economic animal model of Candida albicans (C. albicans) vaginitis. Estrogen benzoate (E2) was given to mice at different concentrations ranging from 0.0 to 0.05 mg/mouse (4 levels) beginning 72 h prior to vaginal inoculation, then mice were in- oculated intravaginally with various concentrations of stationary-phase C. albicans blastoconidia (ATCC90028) (5 levels) in 20 μL of phosphate-buffered saline (PBS) in each E2 level. General state, scores of genital pathology, the hyphae and vaginal fungal burden (CFU) in vaginal lavage fluid, the hydrops rate of uterus and vaginal tissues for pathological section in mice were observed and ob- tained at day 2, 4, 7, 14 and 21 after inoculation. The results showed the infection rate in mice was related to the dosage of E2 and concentration of C. albicans blastoconidia. Additionally there was better cross-effect between the two treated factors. The infection rate was about 80% on the day 4, and could reach 100% on the day 7 until the end of experiment after inoculated intravaginally in groups of E2I3, E2 0.025 mg/mouse injected hypodermically and inoculated intravaginally with 5×104 C. albicans blastoconidia, and large amount of hyphae and blastoconidia could be observe in superfi- cial layer tissue and canal of vaginal by PAS. From the results in our experiment it was concluded that E2I3 was the optima construction condition in kunming mice.
基金This project was supported by grants from the Science Research Foundation of Health Department of Hubei Province (No. JXIB048)the Janssen Research Foundation
文摘To compare the therapeutic effects of three different anti-fungal drugs (i.e., terbinafine, fluconazole and intraconazole) in the treatment of experimental vaginitis caused by Candida albicans (C. albicans) in mice, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans after the animal had been pretreated with estradiol. Mice were divided at random into different groups and then respectively treated with terbinafine, fluconazole and intraconazole given by gastrogavage. The burden of the fungus in the vaginal lavage fluids in the mice of the different groups was measured dynamically at different time points after the beginning of the drug treatment. The fungal burdens in the vaginal lavage fluids taken at different time points from the mice treated with terbinafine were significantly higher than those taken at corresponding time points from mice treated with fluconazole or itraconazole (P〈0.01). The fungal burdens in the vaginal lavage fluids taken from mice 1 week after the beginning of the treatment with terbinafine remained at a relatively high level. A dramatic drop in the fungal burden was noted in the vaginal lavage fluids taken on the 2nd day of the treatment from mice treated with itraconazole or fluconazole group and the fungal burden on the 3rd day of the treatment in these mice were at a very low level, suggesting that fluconazole or itraconazole were highly effective for the treatment. However, the difference in the therapeutic effect between the two drugs was not significant (P〉0.05). Itraconazole or fluconazole, but not terbinafine, is very effective for the treatment of fungal vaginitis caused by C. albicans in mice.
基金financially supported by the National Natural Science Foundation of China [81273409]the Program for Changjiang Scholars and Innovative Research Team in University [IRT_15R37]the Ministry of Science and Technology of China [2017YFA0205301]
文摘Objective To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid(BDSF) and fluconazole(FLU) or itraconazole(ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo. Methods Minimum inhibitory concentrations(MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction(qR T-PCR). Results BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ≤ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qR T-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mR NA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis. Conclusion The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.
基金Supported by Grants from the Brazilian Agencies:CNPq(Conselho Nacional de Desenvolvimento Científico e Tecnológico)CAPES(Coordenao de Aperfeioamento Pessoalde Nível Superior)+1 种基金FAPERJ(Fundao Carlos Chagas Filhode Amparoà Pesquisa do Estado do Rio de Janeiro)supported by a CNPq fellowship
文摘Cells of Candida albicans(C.albicans) can invade humans and may lead to mucosal and skin infections or to deep-seated my coses of almost all inner organs,especially in immunocompromised patients.In this context,both the host immune status and the ability of C.albicans to modulate the expression of its virulence factors are relevant aspects that drive the candidal susceptibility or resistance;in this last case,culminating in the establishment of successful infection knownas candidiasis.C.albicans possesses a potent arma-mentarium consisting of several virulence moleculesthat help the fungal cells to escape of the host immuneresponses.There is no doubt that the secretion of aspartyl-type proteases,designated as Saps,are one of the major virulence attributes produced by C.albicans cells,since these hydrolytic enzymes participate in a wide range of fungal physiological processes as well as in different facets of the fungal-host interactions.For these reasons,Saps clearly hold promise as new potential drug targets.Corroborating this hypothesis,the introduction of new anti-human immunodeficiency virus drugs of the as party l protease inhibitor-type(HIV PIs) have emerged as new agents for the inhibition of Saps.The introduction of HIV PIs has revolutionized the treatment of HIV disease,reducing opportunistic infections,especially candidiasis.The attenuation of candidal infections in HIV-infected individuals might not solely have resulted from improved immunological status,but also as a result of direct inhibition of C.albicans Saps.In this article,we review updates on the beneficial effects of HIV PIs against the human fungal pathogen C.albicans,focusing on the effects of these compounds on Sap activity,growth behavior,morphological architecture,cellular differentiation,fungal adhesion to animal cells and abiotic materials,modulation of virulence factors,experimental candidiasis infection,and their synergistic actions with classical antifungal agents.