Determination of the prevalence of potentially azole-resistant airborne fungi in the Basque Country and the underlying mechanisms in Aspergillus fumigatus
- Autores: Saioa Cendón Sánchez
- Directores de la Tesis: Aitor Rementería Ruiz (dir. tes.), Ana Abad Díaz de Cerio (codir. tes.)
- Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2025
- Idioma: inglés
- Programa de doctorado: Programa de Doctorado en Inmunología, Microbiología y Parasitología / Immunology, Microbiology and Parasitology por la Universidad del País Vasco/Euskal Herriko Unibertsitatea
- Menciones:
- Internacional
- Calificación: Sobresaliente Cum Laude
- Materias:
- Enlaces
- Tesis en acceso abierto en: ADDI
- Resumen
Airborne fungi are ubiquitous microorganisms in the environment, and some of them are recognised as opportunistic pathogens. In clinical settings, infections caused by these species are primarily treated with azoles, while structurally similar agents are also employed in agriculture to control phytopathogenic fungi. This dual use of azole compounds has contributed to rising resistance rates, which have recently become a critical global concern.
Due to the possible environmental origin of azole resistance and the absence of data in the Basque Country, four environmental samplings were conducted to assess the prevalence and diversity of potentially resistant fungi capable of growing at human body temperature, across three areas (hospital surrounding, rural, and urban) located in the three provinces of our community (Araba, Bizkaia and Gipuzkoa). 321 potentially resistant isolates were identified, with Alternaria and Talaromyces being the predominant genera. Overall, the two coastal provinces (Bizkaia and Gipuzkoa) showed the most similarity. Besides, the rural area exhibited the highest alpha diversity for each province, while samples from this area were more alike in terms of beta diversity.
Among airborne fungi, 20 Aspergillus fumigatus isolates were identified, detecting three resistant isolates harbouring the previously described combined mutations TR34/L98H. To assess the ability of susceptible strains to adapt to azoles, four strains were exposed to increasing voriconazole concentrations. Besides, whole-genome sequencing was performed to genetically characterise some of the isolates and to investigate the mechanisms underlying the increased minimal inhibitory concentrations in the adapted strains, which also carried the TR34/L98H mutations.
Three putative multidrug transporters were identified, along with a duplication in the transcription factor SrbA, which regulates the azole target gene. Gene expression analysis in presence of voriconazole suggested that the additional srbA copy, which appeared to be functional, may play a role in azole resistance.
Together, the findings from this thesis provide valuable information of the prevalence of environmental potentially azole-resistant isolates from the Basque Country, including the opportunistic pathogen A. fumigatus, and highlights the importance of performing surveillance studies to monitor antifungal resistance. Nevertheless, further research is required to determine the contribution of the srbA duplication in azole resistance.
