CARLOS PELLESCHI TABORDA
Projetos de Pesquisa
Unidades Organizacionais
BMM, ICB - Docente
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina - Líder
10 resultados
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- Editorial: Tropical fungal diseases(2022) TABORDA, Carlos P.; MUNOZ, Julian Esteban; GONZALEZ, Angel
- In Vitro Antifungal Activity of LL-37 Analogue Peptides against Candida spp.(2022) PINILLA, Gladys; CORONADO, Yenifer Tatiana; CHAVES, Gabriel; MUNOZ, Liliana; NAVARRETE, Jeannette; SALAZAR, Luz Mary; TABORDA, Carlos Pelleschi; MUNOZ, Julian E.Fungal infections have increased in recent decades with considerable morbidity and mortality, mainly in immunosuppressed or admitted-to-the-ICU patients. The fungal resistance to conventional antifungal treatments has become a public health problem, especially with Candida that presents resistance to several antifungals. Therefore, generating new alternatives of antifungal therapy is fundamental. One of these possibilities is the use of antimicrobial peptides, such as LL-37, which acts on the disruption of the microorganism membrane and promotes immunomodulatory effects in the host. In this study, we evaluated the in vitro antifungal activity of the LL-37 analogue peptides (AC-1, LL37-1, AC-2, and D) against different Candida spp. and clinical isolates obtained from patients with vulvovaginal candidiasis. Our results suggest that the peptides with the best ranges of MICs were LL37-1 and AC-2 (0.07 mu M) against the strains studied. This inhibitory effect was confirmed by analyzing the yeast growth curves that evidenced a significant decrease in the fungal growth after exposure to LL-37 peptides. By the XTT technique we observed a significant reduction in the biofilm formation process when compared to yeasts untreated with the analogue peptides. In conclusion, we suggest that LL-37 analogue peptides may play an important antimicrobial role against Candida spp.
- Glucosylceramides From Lomentospora prolificans Induce a Differential Production of Cytokines and Increases the Microbicidal Activity of Macrophages(2019) XISTO, Mariana Ingrid Dutra da Silva; HENAO, Julian Esteban Munoz; DIAS, Lucas dos Santos; SANTOS, Giulia Maria Pires; CALIXTOL, Renata de Oliveira Rocha; BERNARDINO, Mariana Collodetti; TABORDA, Carlos Pelleschi; BARRETO-BERGTER, ElianaLomentospora prolificans is an emerging opportunistic fungus with a high resistance to antifungal agents and it can cause localized infections in immunocompetent patients and disseminated infections with a high mortality rate in immunosuppressed patients. Glucosylceramides (GlcCer) are synthetized in the majority of known fungal pathogens. They are bioactive molecules presenting different functions, such as involvement in fungal growth and morphological transitions in several fungi. The elucidation of the primary structure of the fungal surface glycoconjugates could contribute for the understanding of the mechanisms of pathogenicity. In this work, GlcCer species were isolated from mycelium and conidia forms of L. prolificans and their chemical structures were elucidated by mass spectrometry (ESI-MS). GIcCer purified from both forms presented a major species at m/z 750 that corresponds to N-2-hydroxyhexadecanoyl-1-beta-D-glucopyranosyl-9-methyl-4,8-sphingadienine. Monoclonal antibodies against GlcCer could recognize L. prolificans GIcCer species from mycelium and conidia, suggesting a conserved epitope in fungal GlcCer. In addition, in vivo assays showed that purified GlcCer species from both forms was able to induce a high secretion of pro-inflammatory cytokines by splenocytes. GlcCer species also promote the recruitment of polymorphonuclear, eosinophils, small peritoneal macrophage (SPM) and mononuclear cells to the peritoneal cavity. GlcCer species were also able to induce the oxidative burst by peritoneal macrophages with NO and superoxide radicals production, and to increase the killing of L. prolificans conidia by peritoneal macrophages. These results indicate that GlcCer species from L. prolificans are a potent immune response activator.
- Antifungal Activity of the Biphosphinic Cyclopalladate C7a against Candida albicans Yeast Forms In Vitro and In Vivo(2017) MUNOZ, Julian E.; ROSSI, Diego C. P.; ISHIDA, Kelly; SPADARI, Cristina C.; MELHEM, Marcia S. C.; GARCIA, Daniel M.; CAIRES, Antonio C. F.; TABORDA, Carlos P.; RODRIGUES, Elaine G.Vulvovaginal and invasive candidiasis are frequent conditions in immunosuppressed individuals caused by Candida albicans and non-albicans Candida spp. Fluconazole and Amphotericin B are the main drugs used to fight the infection. However, resistance to fluconazole and other azole antifungal drugs is an important clinical problem that encourages the search for new therapeutic alternatives. In this work, we evaluate the antifungal activity of the biphosphinic cyclopalladate C7a in the in vitro and in vivo model. Our results showed fungicidal activity, with low values of minimal inhibitory concentrations and minimum fungicidal concentrations, even for fluconazole and/or miconazole resistant Candida isolates. Fluorescence microscopy and transmission electron microscopy revealed that the compound was able to inhibit the formation of hyphae/pseudohyphae and, moreover, promoted morphological alterations in cellular organelles and structures, such as disruption of cell wall, apparent mitochondrial swelling, chromatin marginalization into the nuclei and increased numbers of electronlucent vacuoles. C7a significantly decreased the biofilm formation and reduced the viability of yeast cells in mature biofilms when tested against a virulent C. albicans strain. In vivo assays demonstrated a significant decrease of fungal burden in local (vaginal canal) and disseminated (kidneys) infection. In addition, we observed a significant increase in the survival of the systemically infected animals treated with C7a. Our results suggest C7a as a novel therapeutic agent for vaginal and disseminated candidiasis, and an alternative for conventional drug-resistant Candida.
- Editorial: Pathogenesis of Dimorphic Fungal Infections(2021) GONZALEZ, Angel; TABORDA, Carlos P.
- In Vitro and In Vivo Inhibitory Activity of Limonene against Different Isolates of Candida spp.(2020) MUNOZ, Julian E.; ROSSI, Diego C. P.; JABES, Daniela L.; BARBOSA, David Aciole; CUNHA, Fernanda E. M.; NUNES, Luiz R.; ARRUDA, Denise C.; TABORDA, Carlos PelleschiCommensal yeast from the genus Candida is part of the healthy human microbiota. In some cases, Candida spp. dysbiosis can result in candidiasis, the symptoms of which may vary from mild localized rashes to severe disseminated infections. The most prevalent treatments against candidiasis involve fluconazole, itraconazole, miconazole, and caspofungin. Moreover, amphotericin B associated with prolonged azole administration is utilized to control severe cases. Currently, numerous guidelines recommend echinocandins to treat invasive candidiasis. However, resistance to these antifungal drugs has increased dramatically over recent years. Considering this situation, new therapeutic alternatives should be studied to control candidiasis, which has become a major medical concern. Limonene belongs to the group of terpene molecules, known for their pharmacological properties. In this study, we evaluated in vitro the limonene concentration capable of inhibiting the growth of yeast from the genus Candida susceptible or resistant to antifungal drugs and its capacity to induce fungal damage. In addition, intravaginal fungal infection assays using a murine model infected by Candida albicans were carried out and the fungal burden, histopathology, and scanning electron microscopy were evaluated. All of our results suggest that limonene may play a protective role against the infection process by yeast from the genus Candida.
- Pathogenicity Levels of Colombian Strains of Candida auris and Brazilian Strains of Candida haemulonii Species Complex in Both Murine and Galleria mellonella Experimental Models(2020) MUNOZ, Julian E.; RAMIREZ, Laura M.; DIAS, Lucas dos Santos; RIVAS, Laura A.; RAMOS, Livia S.; SANTOS, Andre L. S.; TABORDA, Carlos P.; PARRA-GIRALDO, Claudia M.Candida auris and Candida haemulonii complex (C. haemulonii, C. haemulonii var. vulnera and C. duobushaemulonii) are phylogenetically related species that share some physiological features and habits. In the present study, we compared the virulence of these yeast species using two different experimental models: (i) Galleria mellonella larvae to evaluate the survival rate, fungal burden, histopathology and phagocytosis index and (ii) BALB/c mice to evaluate the survival. In addition, the fungal capacity to form biofilm over an inert surface was analyzed. Our results showed that in both experimental models, the animal survival rate was lower when infected with C. auris strains than the C. haemulonii species complex. The hemocytes of G. mellonella showed a significantly reduced ability to phagocytize the most virulent strains forming the C. haemulonii species complex. Interestingly, for C. auris, it was impossible to measure the phagocytosis index due to a general lysis of the hemocytes. Moreover, it was observed a greater capability of biofilm formation by C. auris compared to C. haemulonii species complex. In conclusion, we observed that C. auris and C. haemulonii complex have different levels of pathogenicity in the experimental models employed in the present study.
- Melanin as a Virulence Factor in Different Species of Genus Paracoccidioides(2020) EMIDIO, ElUzia C. P.; J, Martha E. Uran; SILVA, Leandro B. R.; DIAS, Lucas S.; DOPRADO, Mariana; NOSANCHUK, Joshua D.; TABORDA, Carlos PelleschiParacoccidioidomycosis (PCM) is a granulomatous systemic mycosis caused by the thermo-dimorphic fungi of the genus Paracoccidioides. Melanin production by fungi can affect their pathogenesis and virulence. This study evaluates the production of melanin by different isolates of genus Paracoccidioides and examines how the presence of this polymer affects yeast cell phagocytosis, as well as laccase enzyme production. The results obtained showed that the isolates of genus Paracoccidioides: P. lutzii (Pb01, Pb66, ED01, Pb1578, and Pb8334), P. restrepiensis (PS3-Pb60855), P. brasiliensis (S1-Pb18), and P. americana (PS2-Pbcao) produce melanin in the presence of L-3,4-dihydroxyphenylalanine (L-DOPA). Phagocytosis assays were carried out with peritoneal macrophages from C57Bl/6 mice that were challenged with Pb18, Pb60855, and Pb01. We observed that melanin interferes with phagocytosis in the presence or absence of complement or heat-inactivated serum. This article confirms that different species of the genus Paracoccidioides produce melanin in different magnitudes and that the polymer functions as a virulence factor.
- Repositioning Lopinavir, an HIV Protease Inhibitor, as a Promising Antifungal Drug: Lessons Learned from Candida albicans-In Silico, In Vitro and In Vivo Approaches(2021) SANTOS, Andre L. S.; BRAGA-SILVA, Lys A.; GONCALVES, Diego S.; RAMOS, Livia S.; OLIVEIRA, Simone S. C.; SOUZA, Lucieri O. P.; OLIVEIRA, Vanessa S.; LINS, Roberto D.; PINTO, Marcia R.; MUNOZ, Julian E.; TABORDA, Carlos P.; BRANQUINHA, Marta H.The repurposing strategy was applied herein to evaluate the effects of lopinavir, an aspartic protease inhibitor currently used in the treatment of HIV-infected individuals, on the globally widespread opportunistic human fungal pathogen Candida albicans by using in silico, in vitro and in vivo approaches in order to decipher its targets on fungal cells and its antifungal mechanisms of action. Secreted aspartic proteases (Saps) are the obviously main target of lopinavir. To confirm this hypothesis, molecular docking assays revealed that lopinavir bound to the Sap2 catalytic site of C. albicans as well as inhibited the Sap hydrolytic activity in a typically dose-dependent manner. The inhibition of Saps culminated in the inability of C. albicans yeasts to assimilate the unique nitrogen source (albumin) available in the culture medium, culminating with fungal growth inhibition (IC50 = 39.8 mu M). The antifungal action of lopinavir was corroborated by distinct microscopy analyses, which evidenced drastic and irreversible changes in the morphology that justified the fungal death. Furthermore, our results revealed that lopinavir was able to (i) arrest the yeasts-into-hyphae transformation, (ii) disturb the synthesis of neutral lipids, including ergosterol, (iii) modulate the surface-located molecules, such as Saps and mannose-, sialic acid- and N-acetylglucosamine-containing glycoconjugates, (iv) diminish the secretion of hydrolytic enzymes, such as Saps and esterase, (v) negatively influence the biofilm formation on polystyrene surface, (vi) block the in vitro adhesion to epithelial cells, (vii) contain the in vivo infection in both immunocompetent and immunosuppressed mice and (viii) reduce the Sap production by yeasts recovered from kidneys of infected animals. Conclusively, the exposed results highlight that lopinavir may be used as a promising repurposing drug against C. albicans infection as well as may be used as a lead compound for the development of novel antifungal drugs.
- The secreted acid trehalase encoded by the CgATH1 gene is involved in Candida glabrata virulence(2020) LOPES, Rafael G.; MUNOZ, Julian E.; BARROS, Ludmila M.; ALVES-JR, Sergio L.; TABORDA, Carlos P.; STAMBUK, Boris U.BACKGROUND Candida glabrata yeast is the second cause of candidiasis worldwide. Differs from other yeasts since assimilates only glucose and trehalose (a characteristic used in rapid identification tests for this pathogen) by secreting into the medium a highly active acid trehalase encoded by the CgATH1 gene. OBJECTIVE This study aimed to characterise the function of the acid trehalase in the physiopathology of C. glabrata. METHODS Gene deletion was performed to obtain a mutant ath1 Delta strain, and the ability of the ath1 Delta strain to grow in trehalase, or the presence of trehalase activity in the ath1 Delta yeast cells, was verified. We also tested the virulence of the ath1 Delta strain in a murine model of infection. FINDINGS The ath1 Delta mutant strain grows normally in the presence of glucose, but loses its ability to grow in trehalose. Due to the high acid trehalase activity present in wild-type cells, the cytoplasmic neutral trehalase activity is only detected in the ath1 Delta strain. We also observed a significantly lower virulence of the ath1 Delta strain in a murine model of infection with either normal or immunocompromised mice. MAIN CONCLUSIONS The acid trehalase is involved in the hydrolysis of external trehalose by C. glabrata, and the enzyme also plays a major virulence role during infectivity.