Candida albicans and C. dubliniensis are related yeasts that differ in the expression of virulence-associated proteins involved in adherence and biofilm development. CR3-RP (complement receptor 3-related protein) is one of the surface antigens expressed by Candida species. The main objective of this research was to elucidate the effect of the polyclonal anti-CR3-RP antibody (Ab) on adherence and the biofilm formed by C. albicans SC5314 and C. dubliniensis CBS 7987 and two clinical isolates in vitro, ex vivo and in vivo. A comparison of species, and of treated vs. non-treated with the anti-CR3-RP Ab showed a reduction in adherence (22%-41%) that was dependent on the time point of evaluation (60, 90 or 120 min), but did not prove to be species-dependent. Confocal microscopy revealed a decreased thickness in biofilms formed by both species after pre-treatment with the anti-CR3-RP Ab. This observation was confirmed ex vivo by immunohistochemistry analysis of biofilms formed on mouse tongues. Moreover, anti-CR3-RP Ab administration, 1 h post-infection, has been shown to promote larval survival compared to the control group in a Galleria mellonella infection model. Our data suggest a potential activity of the anti-CR3-RP Ab relevant to immunotherapy or vaccine development against biofilm-associated Candida infections.
This research studied the effectiveness of the photoactive compound methylene blue (MB) activated with red LED light (576-672 nm) compared to that of caspofungin (CAS) on 1 Candida albicans and 3 Candida parapsilosis strains. Results were evaluated in terms of SMIC50 for CAS or in PDI (photodynamic inactivation)-SMIC50 for MB (minimal inhibitory concentration inhibiting sessile biofilm to 50% in comparison to the control without CAS or after irradiation in comparison to the control without MB). While all strains were susceptible to CAS in planktonic form, the SMIC50 was determined to be >16 μg mL(-1) when CAS was added to a 24 h biofilm. However, PDI-MIC50s (1.67 mW cm(-2) , fluence 15 J cm(-2) ) were 0.0075-0.03 mmol L(-1) . For biofilm, PDI-SMIC50s were in the range from 0.7 to 1.35 mmol L(-1) . MB concentration of 1 mmol L(-1) prevented a biofilm being formed ex vivo on mouse tongues after irradiation regardless of the application time, in contrast to CAS, which was only effective at a concentration of 16 μg mL(-1) when it was added at the beginning of biofilm formation. PDI seems to be a promising method for the prevention of microbial biofilms that do not respond significantly to conventional drugs.
In vitro evaluation of specific anti-Candida albicans sera antibodies based on synthetically prepared complement receptor 3-related protein (CR3-RP) mimicking the structure of native complement receptor 3 in a cohort of 72 patients with atopy and recurrent Candida vulvovaginitis (RVC) revealed effective humoral response against Candida CR3-RP. The most significant have been IgM and IgA isotype antibodies (33 and 47% positive cases, respectively). The quantitative evaluation of anti-CR3RP isotype antibodies was confronted with results of commercial ELISA anti-C. albicans antibodies diagnostics based on C. albicans cell wall mannan and β-glucan antigens, the most significant correlation being observed with anti-CR3-RP IgM and anti-β-D-glucan IgM (r(2) = 0.624) followed by isotype IgA (r(2) = 0.381). The immunogenicity and immunoreactivity of CR3RP antigen in RVC patients' sera had been evaluated with regard to the results reached by counterimmunoelectrophoresis and heterogeneous enzyme immunoassay. Obviously, synthetically prepared CR3-RP mimicking the Candida cell-wall-derived structure moiety represents a promising immunological tool not only for Candida serodiagnostics, but also prospectively for follow-up of targeted antifungal therapy and as promising Candida vaccine candidate.
Introduction:Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes. Cladophialophora bantiana is one of the most common and dangerous neurotropic fungi, able to cause brain abscess and disseminated infection.Case Presentation:We report a new case of phaeohyphomycosis brain abscesses caused by C. bantiana in Slovakia. The patient was a 63-year-old man having undergone heart transplantation, with dyspnoea, left-sided bronchopneumonia and fevers. CT (computed tomography) and MRI (magnetic resonance imaging) of the brain revealed numerous abscesses. Bacterial infection was proven by neither the growth of bacteria in culture nor the presence of bacterial antigens. Direct microscopy of the pus from the brain abscess showed Gram-positive hyphae. The isolate was finally identified as C. bantiana based on morphological and physiological features, and on DNA sequence analysis.Conclusion:In spite of appropriate therapy, neurological complications and accelerated respiratory insufficiency resulted in the patient’s death. Concerning clinical manifestation of the brain phaeohyphomycosis that can sometimes be a problem to distinguish from malignancy, physicians should also assume infection caused by this serious pathogen.
The formation of fungal biofilms remains a serious medical problem. In particular, once biofilms are formed, they display high levels of resistance against most common antifungals. Candida albicans and Candida dubliniensis are closely related organisms with respect to morphology and phylogeny, but differ in their expression of virulence-associated proteins involved in adherence and biofilm development. Complement receptor 3-related protein (CR3-RP) is one of the key surface antigens expressed by many pathogenic Candida species associated with adherence and biofilm formation.The main objective of this research was to investigate the role of the polyclonal antibody (Ab) directed against antigen CR3-RP in the inhibition of biofilm formation of C. albicans and C. dubliniensis using different in vitro, ex vivo and in vivo models, and to assess a potential effect of Ab treatment on preformed biofilm of both species.
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