Study and characterization of azole resistance in Aspergillus section Nigri

Identifier:  TDX:3337

Handle: https://hdl.handle.net/20.500.11797/TDX3337

Authors:  Pérez Cantero, Alba

Abstract:
Several species of Aspergillus display clinical relevance, since they are opportunistic pathogens associated to a broad variety of human conditions. Among these, invasive aspergillosis is the most severe in terms of morbidity and mortality. Although Aspergillus fumigatus is the most common causal agent of invasive disease, elevated prevalence of species from other sections, such as section Nigri members, has been reported lately in the clinical field. Despite the current treatment of choice for aspergillosis is voriconazole, azole resistance events have alarmingly increased in the last years, critically impairing disease management. In this context, whereas azole resistance mechanisms in A. fumigatus have been extensively studied, azole resistance in non-fumigatus species remains poorly investigated. On this basis, we aimed to characterize azole resistance in species of Aspergillus section Nigri. With this purpose, we have determined azole susceptibility in section Nigri strains, and we have carried out molecular and genetic analyses of the azoles target proteins, encoded by the cyp51 genes. In addition, ergosterol content and properties of plasma membrane and cell wall have been investigated. Finally, potential resistance mechanisms related to drug degradation and the association between azole resistance and in vitro macrophage phagocytosis were evaluated. Our results diverge from those described in A. fumigatus, which evidences the complexity around resistance mechanisms, especially in non-fumigatus species of Aspergillus.