In the Candida albicans (a pathogenic fungus) infection, Th2 immunity is dominant (A). Thus, tilting Th2 response to Th1 response would be beneficial for treating Candidal infection. In the present ...work, we found that 18β-glycyrrhetinic acid appears to have such immunological activitity
The aim of this study was to determine the immunological adjuvant effect of 18β-glycyrrhetinic acid (GA) isolated from Glycyrrhizae radix. In the experiments, BALB/c mice were immunized on days 1 and 22 intraperitoneally (i.p.) with an emulsion form of Candida albicans surface mannan extract (SM) mixed with either Incomplete Freund's Adjuvant SM/IFA, or Complete Freund's Adjuvant SM/CFA or GA mixed with IFA SM/GA/IFA. One week after the second immunization, polyclonal sera were collected from these animals in order to determine IgG isotypes and cytokine profiles in the sera. After the collection, the spleen samples were collected to determine the degree of T cell proliferation. Additionally, the DTH (delayed type hypersensitivity) response was examined by measuring the footpad swelling of immunized mice. Data resulting from the T cell proliferation test showed that SM/GA/IFA enhanced the proliferation the most. The enhancement was about 85% more compared to SM/IFA (p<0.05). IgG isotypes and cytokine profiles displayed that SM/GA/IFA induced the most abundant production of total IgG with the highest IgG2a/IgG1 ratio (1.31) and greatest IFN-γ secretion. In contrast, SM/CFA resulted in an IgG2a/IgG1 ratio less than 1 and SM/IFA produced a dominant induction of IL-4, but almost no IFN-γ secretion. Together, these observations revealed that GA developed a greater Th1 immune response than Th2 response. The DTH determination confirmed that GA-addition induced dominant Th1 immunity – displaying the highest footpad-swelling followed by SM/CFA and BSA/IFA, respectively. All of this data indicates that GA has a Th1-immunological adjuvant activity, which would be beneficial in the treatment of Th1-disordered disease due to C. albicans.
Resistance to azole antifungals is considered as a significant problem in Candida albicans infections. Several molecular mechanisms of fluconazole resistance including alterations in the gene ...encoding the target enzyme ERG11 or overexpression of efflux pump genes including CDR1, CDR2, MDR1, MDR2 and FLU1 have been reported. The aim of this study was to investigate overexpression of efflux pump genes including CDR1, CDR2, MDR1, MDR2 and FLU1 in fluconazole- resistant C. albicans.
In this study, a total of 97 clinical isolates of C. albicans were isolated from hospitalized children in Children medical center, an Iranian referral hospital. Fluconazole susceptibility testing of C. albicans was performed using the broth microdilution method according to the CLSI guideline. Expression of CDR1, CDR2, MDR1, MDR2 and FLU1 genes was measured using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and 18SrRNA gene was used as a housekeeping gene.
Among 97 C. albicans isolates, 5 strains were categorized as fluconazoleresistant. Overexpression of CDR1, CDR2 and MDR2 genes was found in all isolates. MDR1 overexpression was observed in four resistant isolates. None of the resistant strains displayed increases in FLU1 transcript levels.
Overexpression of the CDR1, CDR2, MDR1 and MDR2 genes might play an important role in fluconazole-resistant C. albicans. No link between expression of FLU1 and fluconazole resistance was found.
Nosocomial fungal infections are important cause of morbidity and mortality in hospital patients. Urinary catheters have been held responsible to cause a large number of hospital acquired Urinary ...Tract Infections (UTIs). This study was undertaken to determine the incidence of nosocomial Candiduria associated with in dwelling urinary catheters, to characterize the species and assess their resistance to antifungal agents.
Urine specimens from 510 catheterized patients were inoculated on Sabauraud Dextrose Agar; the species identification of Candida isolates was done by biochemical tests and antifungal susceptibility testing was done by disc diffusion method.
Candida was isolated in 112 (21.96%) specimens. Of these, Candida albicans was commonly isolated in 50.89% followed by C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, C. guillermondi and C. pseudotropicalis. Fluconazole resistance was encountered in some isolates. All C. glabrata and C. krusei were uniformly resistant to fluconazole and 8 of 16 C. tropicalis were also resistant to it. But only 7 of 57 isolates of C. albicans were resistant to it. Resistance to Nystatin was seen in 34 isolates. Similarly, emergence of resistance was also seen to Ketoconazole and Itraconazole in 24 of 112 isolates. Amphoterecin B resistance was exhibited by 3 C. albicans, 2 C. tropicalis, 1 C. glabrata and 1 C. krusei strain. C. albicans is an important nosocomial pathogen causing UTI in catheterized patients, nevertheless role of other species of Candida as emergent pathogens and resistance to antifungal drugs needs to be emphasized.
An efficient antimicrobial activity was evidenced in a complex β-cyclodextrin-essential oil of Thymus catharinae Camarda (carvacrol chemotype). The release of carvacrol with respect to the ...antimicrobial activity was calculated as function of time. The βCD-complex of the bioactive agent was obtained by a simple, efficient and non-expensive method without purification of the carvacrol chemotype essential oil. According to the starting stoichiometry of β-cyclodextrin with respect to carvacrol, two inclusion complexes were produced, 1:1 and 2:1, respectively. The results demonstrate that, although the antimicrobial activity of the essential oil of T. catharinae Camarda is remarkable but acts too quickly in some types of application, its inclusion in a bio-matrix allows a slower release and improves its effectiveness.
Luliconazole (LZ), a poorly water soluble synthetic imidazole derivative is used in the treatment of fungal infections of skin. Hence, the investigation was aimed at formulating microemulsion based ...gels (MBGs) for solubilization of LZ as well as its better penetration for efficacious anti-fungal treatment. The solubility of LZ in various oils was investigated. Out of tried oils, olive oil exhibited highest solubility. Suitable combination of surfactants and co-surfactants were screened for selected oil to yield O/W type microemulsion. The Pseudoternary phase diagrams were developed to determine microemulsion existence area. The developed microemulsion was evaluated for particle size analysis, isotropicity, pH, drug content and rheology. Drug loaded microemulsion was slowly added to the viscous solution of 1 % Carbomer 934 under magnetic stirring to prepare MBG. The prepared MBG were evaluated in terms of their droplet size, spreadability, stability, in vitro permeation studies, and rheological properties. The phase study revealed that the maximum proportion of oil was incorporated in microemulsion systems when the surfactant-to-cosurfactant ratio was 3:1. The microemulsion was optimized with its components of Olive oil as oil, Capmul MCM as a surfactant and iso propyl alcohol as a cosurfactant. The globule size of the optimized batch was 32.59 nm. The MBG was non-irritant indicating their safety and was active against
C. albicans
indicating its efficacy. Short term stability study performed as per ICH guideline exhibited stable characteristic of developed formulation. Therefore, MBG of LZ is an efficacious treatment for fungal infections.
The research herein includes methodology for eco-friendly preparation of selenium nanoparticles (SeNPs) using the broad-spectrum antibiotic, Megamox (Mega.). Characterization of SeNPs was done using ...UV-Visible spectroscopy, FTIR, XRD, DLS and TEM imaging. Additionally, the immunomodulatory, antioxidant and antimicrobial activities of both SeNPs and Mega. were checked against different strains of bacteria and fungi. TEM and DLS images showed that SeNPs are polydisperse spheres with mean diameter of 22.4 nm. FTIR analysis indicated that the hydroxyl and nitrogen moieties in Mega. were effective for reduction plus binding manner. According to the results of the nitro blue tetrazolium reduction test, both SeNPs and Mega. presented high intracellular killing activity, which confirmed their immunostimulatory effect. Antioxidant activity of SeNPs and Mega. were 90 and 82 %, respectively. SeNPs presented great activity facing multi-drug resistant bacteria and TB. SeNPs are considered promising cost-effective and eco-friendly anti-bacterial and anti-fungal agents that can represent a new potential nano-platform in both medical and infectious diseases control.
In the last few years, several fungus infections caused by multidrug-resistant pathogenic agents have got tremendous emergence and prevalence. Screening for novel antifungal agents is in great ...demand, but traditional microbiological techniques are far from sufficient to meet that requirement. In this study, a non-invasive and non-destructive microcalorimetric method was performed to investigate the antifungal activities of cholic acid (CA) and its derivatives, glycocholic acid (GCA) and taurocholic acid (TCA) on the multiplying and non-multiplying metabolism of
Candida albicans. Then, the heat-flow power-time curves of
C. albicans growth affected by different concentrations of CA, GCA and TCA were studied by similarity analysis (SA), the quantitative thermokinetic parameters from these curves were analyzed by multivariate analysis of variance (MANOVA) and principal component analysis (PCA). By comparing the values of two main parameters,
P
2 (the heat-flow output power of the highest peak) and
Q
2 (the heat output of the second exponential growth phase) of
C. albicans, it could be found that CA had the strongest antifungal activity among the three steroid compounds, which might be used as a potential antifungal agent in the future. This study provided a useful method and idea of microcalorimetry with chemometrics to efficiently evaluate the antifungal activities of bile acid derivatives, giving some references for screening out new antifungal agents.
However, it has to be stressed that all these experiments are carried out
in vitro and they still require clinical validation.
Candida albicans is a major fungal pathogen of humans, causing mucosal infections that are difficult to eliminate and systemic infections that are often lethal primarily due to defects in the host's ...innate status. Here we demonstrate the utility of Caenorhabditis elegans, a model host to study innate immunity, by exploring the role of reactive oxygen species (ROS) as a critical innate response against C. albicans infections. Much like a human host, the nematode's innate immune response is activated to produce ROS in response to fungal infection. We use the C. albicans cap1 mutant, which is susceptible to ROS, as a tool to dissect this physiological innate immune response and show that cap1 mutants fail to cause disease and death, except in bli-3 mutant worms that are unable to produce ROS because of a defective NADPH oxidase. We further validate the ROS-mediated host defense mechanism in mammalian phagocytes by demonstrating that chemical inhibition of the NADPH oxidase in cultured macrophages enables the otherwise susceptible cap1 mutant to resists ROS-mediated phagolysis. Loss of CAP1 confers minimal attenuation of virulence in a disseminated mouse model, suggesting that CAP1-independent mechanisms contribute to pathogen survival in vivo. Our findings underscore a central theme in the process of infection-the intricate balance between the virulence strategies employed by C. albicans and the host's innate immune system and validates C. elegans as a simple model host to dissect this balance at the molecular level.
In this paper the authors investigated a synergistic antimycotic effect between four antifungal drugs Amphotericin B, Fluconazole, Tioconazole, and Flucytosine individually combined with ...Anidulafungin compound. This latter is considered a drug of choice in the treatment of fungal infections; it has good activity both in vitro and in vivo against yeasts and moulds, as Candida and Aspergillus. The goal of this study was to evaluate the in vitro interaction of Anidulafungin in the synergic combinations with previous reported drugs against 12 Candida strains according to CLSI M27-A3 protocol. A synergistic interaction was observed against the most antifungal strains; in particular an increasing of the antimycotic efficacy was obtained from the association between Anidulafungin and Amphotericin B or Fluconazole (Mixture 4:6). In contrast the association Tioconazole/Anidulafungin was less effective on fungal species growth. The antimycotics MIC reduction values were more evident against some strains as C. glabrata, C. krusei, C. tropicalis and C. parapsilosis.
Aims: To study the interactions between Candida albicans and 12 other species of Candida and bacteria in biofilms.
Methods and Results: The number of cells within growing biofilms in a polystyrene ...tube model was measured after adding C. albicans to preformed biofilms of other micro‐organisms and vice versa. It was also measured after simultaneous biofilm formation of C. albicans and other micro‐organisms. The number of cells of C. albicans within the growing biofilms decreased significantly (P < 0·05) when the fungus was added to preformed biofilms of Candida spp. and bacteria except, with C. parapsilosis, Torulopsis glabrata and the glycocalyx producer Pseudomonas aeruginosa. When C. parapsilosis, Staphylococcus epidermidis (nonglycocalyx producer) or Serratia marcescens was added to preformed biofilms of C. albicans, the number of cells of these micro‐organisms increased in the growing biofilms.
Conclusions: Biofilms of C. albicans are capable of holding other micro‐organisms and more likely to be heterogeneous with other bacteria and fungi in the environment and on medical devices.
Significance and Impact of the Study: Recognition of the heterogeneity of biofilm‐associated organisms can influence treatment decisions, particularly in patients who do not respond to initial appropriate therapy.
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