Abstract
The ubiquitous fungal pathogen Aspergillus fumigatus is a mediator of allergic sensitization and invasive disease in susceptible individuals. The significant genetic and phenotypic variability between and among clinical and environmental isolates are important considerations in host-pathogen studies of A. fumigatus-mediated disease. We observed decreased radial growth, rate of germination, and ability to establish colony growth in a single environmental isolate of A. fumigatus, Af5517, when compared to other clinical and environmental isolates. Af5517 also exhibited increased hyphal diameter and cell wall β-glucan and chitin content, with chitin most significantly increased. Morbidity, mortality, lung fungal burden, and tissue pathology were decreased in neutropenic Af5517-infected mice when compared to the clinical isolate Af293. Our results support previous findings that suggest a correlation between in vitro growth rates and in vivo virulence, and we propose that changes in cell wall composition may contribute to this phenotype.
Highlights
Aspergillus fumigatus is a ubiquitous filamentous mold that is associated with pulmonary pathology in patients suffering from asthma, cystic fibrosis, and immune deficiencies [1]
In patients with chronic lung inflammatory diseases such as asthma or cystic fibrosis, inhalation of A. fumigatus can lead to allergic bronchopulmonary aspergillosis (ABPA), which is marked by fungal persistence in the airways and increased inflammatory responses
Af5517 conidia displayed a reduced ability to establish colony growth, our results suggest this is not due to decreased conidial viability, but rather due to limited and/or delayed growth after germination
Summary
Aspergillus fumigatus is a ubiquitous filamentous mold that is associated with pulmonary pathology in patients suffering from asthma, cystic fibrosis, and immune deficiencies [1]. In patients with chronic lung inflammatory diseases such as asthma or cystic fibrosis, inhalation of A. fumigatus can lead to allergic bronchopulmonary aspergillosis (ABPA), which is marked by fungal persistence in the airways and increased inflammatory responses. The most severe disease occurs in neutropenic individuals or patients treated with immune suppressive drugs after hematopoietic stem cell or organ transplantation. These patients are susceptible to development of invasive aspergillosis (IA), a serious infection associated with a high mortality rate [1,4]. Not surprisingly, when studied in experimental models, clinical isolates with higher in vitro growth rates exhibited increased virulence in mice when compared to slower growing isolates [13] or environmental isolates [14,15]. There is a correlation between isolate virulence and in vitro growth rates, specific phenotypic differences that may play a role in this association have yet to be closely examined
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