Antifungal resistance on Sporothrix species: an overview

Abstract

Introduction The treatment of human and animal sporotrichosis is often performed with antifungal agents; however, the emergence of antifungal-resistant strains of Sporothrix species has been reported. We aimed to discuss the ability of Sporothrix species in developing resistance to the conventional antifungals and mechanisms for this. Methodology Published data on databases (PubMed, Science Direct, Google Scholar) were investigated using a combination of keywords from 2008 to 2019 by the StArt tool. Results The minimal inhibitory concentrations values based on the Clinical and Laboratory Standards Institute (CLSI) from eight references were classified according to the epidemiological cutoff values in wild-type or non-wild-type strains. In this way, nonwild-type S. schenckii and, mainly, S. brasiliensis isolates were recognized on itraconazole, amphotericin B, terbinafine, and voriconazole, which are strains that deserve more attention toward antifungal control, with a probable risk of mutation to antifungal resistance. Among the few reviewed studied on antifungal resistance, the melanin production capacity (DHN-melanin, L-DOPA melanin, and pyomelanin), the low genetic diversity due to the abnormal number of chromosomes, and the mutation in cytochrome P450 are some of the factors for developing resistance mechanism. Conclusions The emergence of Sporothrix species with in vitro antifungal resistance was evidenced and the possible mechanisms for resistance development may be due to the melanin production capacity, genetic diversity and mutations in cytochrome P450. Further studies should be carried out targeting gene expression for the development of antifungal resistance on Sporothrix species in order to prospect new therapeutic targets for human and veterinary use.

Identification of two potential inhibitors of Sporothrix brasiliensis and Sporothrix schenckii in the Pathogen Box collection

“…Although sporotrichosis is endemic in several countries, treatment remains restricted to a few options, relying mainly on itraconazole [4]. The emergence of clinical and feline-borne isolates with low in vitro susceptibility to itraconazole and the constantly reported therapeutic failure highlights the need to seek new options for sporotrichosis treatment [9][10][11].…”

Melanin and chromoblastomycosis agents: Characterization, functions, and relation with antifungals

“…In relation to antifungals, melanin is considered an antifungal resistance factor, due to its ability to reduce the susceptibility of melanized cells to these drugs [48]. This is an important factor and there are already studies proposing the use of inhibitors of melanin synthesis to increase the susceptibility of fungi to antifungals [49,50].…”

Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses

“…This azole is hepatotoxic, exclusively administered orally, with a high cost for the affected population, most of which live in socially vulnerable areas [13]. Thus, despite being improved, sporotrichosis therapy remains an unsolved problem since the reduction in S. brasiliensis sensitivity to this azole has been reported [12,14,15]. These authors described S. brasiliensis isolates obtained from patients residing in distinct Brazilian states such as Rio de Janeiro [16][17][18], São Paulo [16], Minas Gerais [18] and Rio Grande do Sul [12,14,19].…”