ABSTRACT
Nosocomial infections by fungi are important causes of morbidity and mortality, and the adhesion capacity of yeast on abiotic and biotic surfaces has been considered an important step in this process. Als3 proteins are widely studied for their ability to allow Candida albicans to bind to various surfaces. The objective of the present study was to verify, with more details, the action of F2768-0318 in relation to its antifungal activity as well as its ability to act on C. albicans virulence factors related to adhesion and biofilm formation in vitro and in vivo by inhibiting the Als3 protein. F2768-0318 was assessed in tests of biofilm formation and adhesion on abiotic surfaces (polystyrene plates) and adherence on biotic surfaces, including human endocervical (HeLa) cells, human umbilical vein endothelial cells (HUVECs), and fresh buccal epithelial cells (BEC). Our results showed F2768-0318 was useful in reducing the adhesion and biofilm formation of C. albicans on abiotic surfaces, indicating the possibility of treating hospital materials and preventing biofilm formation on these types of equipment. Further studies are still needed, including optimization of the molecule to allow this molecule to be effective on other types of surfaces, such as human cells.
Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Animals , Antifungal Agents/therapeutic use , Candida albicans/growth & development , Candida albicans/physiology , Candidemia/drug therapy , Candidemia/microbiology , Cell Adhesion/drug effects , Cells, Cultured , Epithelial Cells/drug effects , Epithelial Cells/microbiology , Epithelial Cells/physiology , Female , HeLa Cells , Human Umbilical Vein Endothelial Cells , Humans , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Toxicity TestsABSTRACT
Following a fatal case of Cryptococcus neoformans meningitis in a child with X-linked hyper-immunoglobulin M syndrome (XHIGM), we evaluated the fungal isolate in an experimental infection in a mouse model with respect to microbiology, epidemiology, virulence and response to therapy. The minimum inhibitory concentrations for antifungals in the susceptibility test were 0.5mg/L for amphotericin B, 4.0mg/L for fluconazole and 0.12mg/L for voriconazole. Evaluation of pathogenicity by means of an experimental infection in BALB/c mice showed that fungus isolated from the blood and cerebrospinal fluid of the child was able to disseminate, reaching the spleen, lungs and brain, where it caused significant macroscopic alterations in the size and texture of each organ. Treatment of infected mice with amphotericin B reduced the fungal load in the spleen and lungs, but not in the brain.
Subject(s)
Cryptococcus neoformans/isolation & purification , Cryptococcus neoformans/pathogenicity , Hyper-IgM Immunodeficiency Syndrome, Type 1/complications , Hyper-IgM Immunodeficiency Syndrome, Type 1/microbiology , Meningitis, Cryptococcal/diagnostic imaging , Meningitis, Cryptococcal/microbiology , Amphotericin B/pharmacology , Animals , Antifungal Agents/pharmacology , Child, Preschool , Cryptococcus neoformans/drug effects , Disease Models, Animal , Fatal Outcome , Humans , Hyper-IgM Immunodeficiency Syndrome, Type 1/diagnosis , Male , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Tomography, X-Ray ComputedABSTRACT
AIM: To investigate the antifungal activity of MOL3, a small molecule that was selected by virtual screening, against Candida spp. MATERIALS & METHODS: The antifungal activity of MOL3 was evaluated using standard strains and clinical isolates. Activity was evaluated in both in vitro tests and animal models. RESULTS: The minimum fungicidal concentration of MOL3 against Candida spp. ranged from 16 to 128 mg/l. MOL3 at the sub-minimum fungicidal concentration inhibited hyphal elongation. The remaining yeast cells presented morphological changes and were metabolically inactive. MOL3 was toxicologically inert both in vitro and in the animal model. MOL3 also reduced experimental systemic infection by C. parapsilosis in mice. CONCLUSION: The selection of MOL3 by virtual screening was successful, revealing a promising antifungal candidate.
Subject(s)
Antifungal Agents/pharmacology , Candida parapsilosis/drug effects , Candidiasis, Invasive/drug therapy , Enzyme Inhibitors/pharmacology , Fungal Proteins/antagonists & inhibitors , Mannosyltransferases/antagonists & inhibitors , Animals , Antifungal Agents/therapeutic use , Computer Simulation , Enzyme Inhibitors/therapeutic use , Male , Mice , Mice, Inbred BALB CABSTRACT
The objective of this study was to investigate tongue coating (TC) frequency and its colonization by yeasts in a group of chronic kidney disease (CKD) patients. Clinical examination of the oral mucosa of 33 CKD patients was performed to investigate oral and tongue lesions. TC was diagnosed according to its clinical characteristics. Stimulated saliva and TC samples were collected to verify the salivary flow, and determine yeast frequency, species and counts. TC was found in 18/33 of the patients (54.55 %) and was the most frequent oral lesion found. Of 18 patients with TC, 13 (72.22 %) presented positive cultures for yeasts on the tongue dorsum, and one (5.55 %) in the saliva only. Yeasts were significantly more frequent in the tongue dorsum when compared to the saliva (p = 0.0106). The most frequent yeast species found was C. albicans (55.55 %), while C. parapsilosis comprised 50 % of non-albicans Candida species. This study demonstrated high amounts of yeasts on the cultures from TC samples of CKD patients, strongly suggesting that TC is a clinical representation of a polymicrobial biofilm, which could serve as a gateway for disseminated infection in immunosuppressed patients undergoing frequent hospitalization.
