Susceptibility of sequential <i>Fonsecaea pedrosoi</i> isolates from chromoblastomycosis patients to antifungal agents

Andrade, Tânia Sueli de; Castro, Luiz Guilherme Martins; Nunes, Ricardo; Gimenes, Viviane Mazo Fávero; Cury, Arlete Emily

doi:10.1111/j.1439-0507.2004.00984.x

Cited by 55 publications

(12 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Terbinafine, itraconazole and voriconazole all showed good sensitivity for the isolate from this case, with the MICs being 0.125, 1 and 0.5 µg/ml, respectively. This also suggested that the determination of in vitro susceptibility profiles may be useful to identify intrinsic microbiologic resistance to antifungal drugs, but does not predict the clinical response [19, 20]. Patients’ status is also the important factors for the treatment effect.…”

Section: Discussionmentioning

confidence: 99%

Photodynamic Therapy Combined with Terbinafine Against Chromoblastomycosis and the Effect of PDT on Fonsecaea monophora In Vitro

Huang

et al. 2014

Mycopathologia

View full text Add to dashboard Cite

Chromoblastomycosis, a chronic fungal infection of skin and subcutaneous tissue caused by dematiaceous fungi, is associated with low cure and high relapse rates. Among all factors affecting clinical outcome, etiological agents have an important position. In southern China, Fonsecaea pedrosoi and Fonsecaea monophora are main causative agents causing Chromoblastomycosis. We treated one case of chromoblastomycosis by photodynamic therapy (PDT) of 5-aminolevulinic acid (ALA) irradiation combined with terbinafine 250 mg a day. The lesions were improved after two sessions of ALA-PDT treatment, each including nine times, at an interval of 1 week, combined with terbinafine 250 mg/day oral, and clinical improvement could be observed. In the following study, based on the clinical treatment, the effect of PDT and antifungal drugs on this isolate was detected in vitro. It showed sensitivity to terbinafine, itraconazole or voriconazole, and PDT inhibited the growth. Both the clinic and experiments in vitro confirm the good outcome of ALA-PDT applied in the inhibition of F. monophora. It demonstrated that combination of antifungal drugs with ALA-PDT arises as a promising alternative method for the treatment of these refractory cases of chromoblastomycosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Photodynamic Therapy Combined with Terbinafine Against Chromoblastomycosis and the Effect of PDT on Fonsecaea monophora In Vitro

Huang

et al. 2014

Mycopathologia

View full text Add to dashboard Cite

show abstract

“…Itraconazole (200–400 mg per day for a long period, usually between 6 and 12 months) is considered as an alternative; however, many patients do not show clinical improvement [6]. For some cases, the best therapeutic strategy in cases of chromoblastomycosis seems to be a combination of two drugs chosen according to the results of prior antifungal susceptibility testing [45], such as the combination of amphotericin B and 5-fluorocytosine, itraconazole and 5-fluorocytosine [46], or itraconazole and terbinafin [47].…”

Section: Discussionmentioning

confidence: 99%

“…Chemotherapy, surgical excision and/or cryosurgery have been used throughout the years [5], [6], but an effective treatment for chromoblastomycosis has not yet been established. Treatment of the mycosis caused by this agent is unrewarding not only because of the scarcity of effective antifungal agents but also due to the need for prolonged periods of treatment, which in some reports has required extended therapeutic regimens of up to 2 years to obtain a mycological cure [7].…”

Section: Introductionmentioning

confidence: 99%

Beneficial Effects of HIV Peptidase Inhibitors on Fonsecaea pedrosoi: Promising Compounds to Arrest Key Fungal Biological Processes and Virulence

Palmeira¹,

Kneipp²,

Rozental³

et al. 2008

PLoS ONE

View full text Add to dashboard Cite

Background Fonsecaea pedrosoi is the principal etiologic agent of chromoblastomycosis, a fungal disease whose pathogenic events are poorly understood. Current therapy for chromoblastomycosis is suboptimal due to toxicity of the available therapeutic agents and the emergence of drug resistance. Compounding these problems is the fact that endemic countries and regions are economically poor.Purpose and Principal FindingsIn the present work, we have investigated the effect of human immunodeficiency virus (HIV) peptidase inhibitors (PIs) on the F. pedrosoi conidial secreted peptidase, growth, ultrastructure and interaction with different mammalian cells. All the PIs impaired the acidic conidial-derived peptidase activity in a dose-dependent fashion, in which nelfinavir produced the best inhibitory effect. F. pedrosoi growth was also significantly reduced upon exposure to PIs, especially nelfinavir and saquinavir. PIs treatment caused profound changes in the conidial ultrastructure as shown by transmission electron microscopy, including invaginations in the cytoplasmic membrane, disorder and detachment of the cell wall, enlargement of fungi cytoplasmic vacuoles, and abnormal cell division. The synergistic action on growth ability between nelfinavir and amphotericin B, when both were used at sub-inhibitory concentrations, was also observed. PIs reduced the adhesion and endocytic indexes during the interaction between conidia and epithelial cells (CHO), fibroblasts or macrophages, in a cell type-dependent manner. Moreover, PIs interfered with the conidia into mycelia transformation when in contact with CHO and with the susceptibility killing by macrophage cells.Conclusions/SignificanceOverall, by providing the first evidence that HIV PIs directly affects F. pedrosoi development and virulence, these data add new insights on the wide-spectrum efficacy of HIV PIs, further arguing for the potential chemotherapeutic targets for aspartyl-type peptidase produced by this human pathogen.

show abstract

“…Even under such treatment, relapses are very common (Santos et al, 2007; Queiroz-Telles and Santos, 2013). Although some antifungals are available for treating chromoblastomycosis they act on relatively few distinct molecular targets and the emergence of resistance is a frequent problem (Andrade et al, 2004). Thus, the search for new targets and novel therapeutic strategies are the primary challenges in the sustained effort to combat this debilitating mycosis.…”

Section: Introductionmentioning

confidence: 99%

HIV Aspartic Peptidase Inhibitors Modulate Surface Molecules and Enzyme Activities Involved with Physiopathological Events in Fonsecaea pedrosoi

et al. 2017

View full text Add to dashboard Cite

Fonsecaea pedrosoi is the main etiological agent of chromoblastomycosis, a recalcitrant disease that is extremely difficult to treat. Therefore, new chemotherapeutics to combat this fungal infection are urgently needed. Although aspartic peptidase inhibitors (PIs) currently used in the treatment of human immunodeficiency virus (HIV) have shown anti-F. pedrosoi activity their exact mechanisms of action have not been elucidated. In the present study, we have investigated the effects of four HIV-PIs on crucial virulence attributes expressed by F. pedrosoi conidial cells, including surface molecules and secreted enzymes, both of which are directly involved in the disease development. In all the experiments, conidia were treated with indinavir, nelfinavir, ritonavir and saquinavir (100 μM) for 24 h, and then fungal cells were used to evaluate the effects of HIV-PIs on different virulence attributes expressed by F. pedrosoi. In comparison to untreated controls, exposure of F. pedrosoi cells to HIV-PIs caused (i) reduction on the conidial granularity; (ii) irreversible surface ultrastructural alterations, such as shedding of electron dense and amorphous material from the cell wall, undulations/invaginations of the plasma membrane with and withdrawal of this membrane from the cell wall; (iii) a decrease in both mannose-rich glycoconjugates and melanin molecules and an increase in glucosylceramides on the conidial surface; (iv) inhibition of ergosterol and lanosterol production; (v) reduction in the secretion of aspartic peptidase, esterase and phospholipase; (vi) significant reduction in the viability of non-pigmented conidia compared to pigmented ones. In summary, HIV-PIs are efficient drugs with an ability to block crucial biological processes of F. pedrosoi and can be seriously considered as potential compounds for the development of new chromoblastomycosis chemotherapeutics.

show abstract

Susceptibility of sequential Fonsecaea pedrosoi isolates from chromoblastomycosis patients to antifungal agents

Cited by 55 publications

References 30 publications

Photodynamic Therapy Combined with Terbinafine Against Chromoblastomycosis and the Effect of PDT on Fonsecaea monophora In Vitro

Photodynamic Therapy Combined with Terbinafine Against Chromoblastomycosis and the Effect of PDT on Fonsecaea monophora In Vitro

Beneficial Effects of HIV Peptidase Inhibitors on Fonsecaea pedrosoi: Promising Compounds to Arrest Key Fungal Biological Processes and Virulence

HIV Aspartic Peptidase Inhibitors Modulate Surface Molecules and Enzyme Activities Involved with Physiopathological Events in Fonsecaea pedrosoi

Contact Info

Product

Resources

About