Aspergillus no contexto One Health: Epidemiologia molecular, resistência a azóis e novos compostos com atividade antifúngica frente a isolados clínicos de humanos e de aves aquáticas

Abstract

The "One health" context considers health on three pillars: animal health, human health and ecosystem health. In this approach, the role of environmental changes in the emergence of chronic and infectious diseases is highlighted, and as a strong ally in the development of disease prevention strategies. Fungi of the Aspergillus genus fit substantially in this approach, in view of their ubiquity, as well as their importance as potential animal and human pathogens. In addition to the intrinsic resistance presented by some species, the emergence of azole resistance acquired by isolates of Aspergillus fumigatus sensu stricto is a concern of the scientific community at a global level. This study aimed to evaluate the molecular epidemiology of clinical isolates of Aspergillus from birds and humans from the south of Rio Grande do Sul, Brazil, and to evaluate the susceptibility profile and mechanisms of azole resistance. As a result, we carried out a wide literature review in the context of One Health, focusing on the role of birds as an environmental indicator and on the dispersion of Aspergillus strains; we first described aspergillosis in albatrosses during rehabilitation; and we describe cases of aspergillosis in free-living aquatic birds. We also obtained important in vitro results on the antifungal activity of the diphenyl diselenide compound alone and in combination with classic antifungals. Regarding the search for azole resistance in A. fumigatus, no mutations related to the environmental context of the emergence of resistance in this fungal species in the region studied in Brazil were detected. In addition, genetic diversity research has shown high diversity in the isolates studied, so it is concluded that the technique used is of great value for the clinical monitoring of patients, in addition to confirming that the animal recovery environment is a potential source of infection for birds (in this case, penguins) during rehabilitation. The detection of the same genotype in A. fumigatus strain isolated in a human patient and a freeliving penguin demonstrated the importance of an Aspergillus and aspergillosis One Health approach, since the same strain has both a potential for colonization / infection in animals as in humans. Finally, as a result of the international partnership established during the development of this work, we had the first report of the resistance mutation TR34 / L98H in an indoor environment in Portugal, and the result of surveillance in Aspergillus carried out by a reference laboratory in Portugal, in which a high prevalence of cryptic species of Aspergillus was found in clinical and environmental isolates, in addition to pan-azole resistance in A. fumigatus strains, confirming the molecular mechanisms involved with antifungal resistance in the cyp51A gene. The results obtained in this work show the importance of the multidisciplinary approach of Aspergillus and aspergillosis, and the need to expand the surveillance of Aspergillus in the context of One Health, in order to better understand the mechanisms involved in the dispersion of strains, and in the adoption of more effective measures to monitoring the emergence of resistance, as well as the adoption of strategies to control the growth of this global problem.