Avaliação da expressão de genes da resposta antioxidante de candida albicans na ausência e presença de concentrações subinibitórias de antifúngicos

Abstract

Invasive fungal infections are considered a serious problem, especially in immunocompromised patients and antifungal treatment. Among these infections, the ones caused by the genus Candida spp., Mainly C. albicans, stand out because of their innumerable factors associated with virulence. These species present numerous factors associated with virulence and the ability to evade the immune system of the host, causing a predominance of infections in the hospital and the community. In the host, phagocytic cells respond to various microbial stimuli with the production of reactive oxygen species (ROS), which are responsible in part for the microbicidal activity of these cells, which act at the protein, lipid, and genetic levels. In the central response to the oxidant environment is the CAP1 gene, which is responsible for the activation of several other genes associated with oxidative stress, and whose requisition for tolerance to the oxidant environment by C. albicans is known. In the course of the antioxidant cascade, other genes are activated, such as those in the SOD family (SOD1-6) and catalase (CAT1), whose functions are to disrupt ROS such as superoxide and to decompose hydrogen peroxide, respectively. The antifungal agents used in the clinic, both for prophylactic or treatment, include amphotericin B, fluconazole and caspofungin, with sensitivity tests being extremely important for effective administration. It has been attributed to these antifungals, as an additional mechanism of action, the increase of ROS production, which may contribute to the positive effect of the treatment, but, on the other hand, may contribute to the increase of resistance of the fungus to these species. This work aimed to evaluate the phagocytosis process and the fungicidal capacity of macrophages in the samples treated with the subinhibitory concentrations of the antifungal agents amphotericin B, fluconazole and caspofungin, as well as the differential expression of CAP1, SOD1-6 and CAT1 genes in C. albicans SC4314, 121 and 221-V by RT-PCR. Treatment with caspofungin promoted the highest expression of practically all genes studied in all isolates, but all antifungal modulates, either positively or negatively, the relative expression of all genes. Pre-treatment with caspofungin appears to have protected the fungus from macrophage attack. Treatment with subinhibitory doses promotes several types of stress, among them oxidative, which causes alterations in the transcription profile of the antioxidant response genes and this may favor the fungus in the fight against the immune system of the host, being able to directly influence the therapy or antifungal prophylaxis of invasive fungal diseases of medical interest.