Revealing virulence potential of clinical and environmental Aspergillus fumigatus isolates using Whole-genome sequencing

Abstract

39Aspergillus fumigatus is an opportunistic airborne pathogen and the most common causative 40 agent of human fungal infections. A restricted number of virulence factors have been 41 described but none of them lead to a differentiation of the virulence level among different 42 strains. In this study, we analyzed the whole-genome sequence of a set of A. fumigatus isolates 43 from clinical and environmental origin to compare their genomes and to determine their 44 virulence profiles. For this purpose, a database containing 244 genes known to be associated 45 with virulence was built. The genes were classified according to their biological function into 46 factors involved in thermotolerance, resistance to immune responses, cell wall structure, 47 toxins and secondary metabolites, allergens, nutrient uptake and signaling and regulation. No 48 difference in virulence profiles was found between clinical isolates causing an infection and a 49 colonizing clinical isolate, nor between isolates from clinical and environmental origin. We 50 observed the presence of genetic repetitive elements located next to virulence related gene 51 groups, which could potentially influence their regulation. In conclusion, our genomic analysis 52 reveals that A. fumigatus, independently of their source of isolation, are potentially pathogenic 53 at the genomic level, which may lead to fatal infections in vulnerable patients. However, other 54 determinants such as genetic variations in virulence related genes and host-pathogen 55 interactions most likely influence A. fumigatus pathogenicity and further studies should be 56 performed. 57 58 Importance 59 Aspergillus spp. infections are among the most clinically relevant fungal infections also 60 presenting treatment difficulties due to increasing antifungal resistance. The lack of key 61 virulence factors and a broad genomic diversity complicates the development of targeted 62 diagnosis and novel treatment strategies. A widely spread variability in virulence has been 63 reported for experimental, clinical and environmental isolates. Here we provide supporting 64 evidence that members of this species are fully capable of establishing an infection in 65 immunosuppressed hosts according to their virulence content at the genomic level. Due to the 66 possible clinical complications, studies are urgently required linking strain's virulent 67 phenotype with the genotype to better understand the virulence activation of this important 68 fungal pathogen. 69 70 71 Results 131Virulence related genes screening showed that all A. fumigatus isolates included in this 132 study are potentially pathogenic. The genome sequences of nine A. fumigatus isolates 133 (Table 1) were screened for the presence of particular VRGs using our in-house database (see 134 Table S2). We identified the presence of all 244 VRGs (>90% coverage and >90% identity) in 135 the genome of seven isolates P1MR, P1MS, P2CS, Af293, 12-7505054, 08-19-02-30 and 08-19-136 02-46. In addition, 243 genes were present in the genomes of B5233 ...

Increased production of pathogenic, airborne fungal spores upon exposure of a soil mycobiota to chlorinated aromatic hydrocarbon pollutants

“…For example, A fumigatus strain-speci c virulence is known to be modulated by nitrogen metabolism 40 (clearly dysregulated during PCP degradation 21 ) and by the ability to thrive in low oxygen conditions 39 . The observed heterogeneity raises questions as to which genetic/epigenetic mechanisms contribute more to pathogenicity across human fungal pathogens and which are clinically relevant 53 , but to date this remains largely unknown. Our study shows that soil pollution can promote an increase in the virulence of airborne spores of Aspergillus spp.…”

Aspergillus fumigatus: análisis microscópico de su estructura en un modelo de biofilm in vitro

“…En esta línea, algunos autores han sugerido en estudios previos que la variabilidad intraespecie en A. fumigatus conlleva diferencias en la capacidad patogénica [7,8]. Si bien, otros como el descrito por Puértolas-Balint y col., no encuentran diferencias en virulencia entre cepas cuando se analizan aislados clínicos y ambientales de A. fumigatus [9]. estas discrepancias pueden estar relacionadas con la capacidad de formar biofilms y con la fase de desarrollo del mismo en la que se evalúa el efecto virulento.…”

Galleria mellonella as a screening tool to study virulence factors of Aspergillus fumigatus

“…In the same way, Knox et al . showed that two A. fumigatus isolates collected in the International Space Station were more lethal than the clinical reference strain in zebrafish model [ 83 ].…”