Isolate-Dependent Growth, Virulence, and Cell Wall Composition in the Human Pathogen Aspergillus fumigatus

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.

Characterization of Aspergillus fumigatus Isolates from Air and Surfaces of the International Space Station

“…2B), which is consistent with previous reports of strain-dependent variations in growth rates of A. fumigatus isolates (21) as well as increased biomass production for some microbes during exposure to space environments (32). As early spore germination rates may favor niche exploitation and establishment of robust growth (21), we next sought to determine whether ISS isolates exhibited different germination dynamics in vitro . Figure 2C shows there were no differences in germination rates between ISSFT-021, IF1SW-F4, and CEA10 in liquid GMM, as nearly all spores germinated after an 8-h incubation, while Af293 showed a marked delay in germination.…”

“…An examination of radial growth rates revealed that both ISS strains significantly outgrew both Af293 and CEA10 at all time points investigated (Fig. 2B), which is consistent with previous reports of strain-dependent variations in growth rates of A. fumigatus isolates (21) as well as increased biomass production for some microbes during exposure to space environments (32). As early spore germination rates may favor niche exploitation and establishment of robust growth (21), we next sought to determine whether ISS isolates exhibited different germination dynamics in vitro .…”

“…Likely underlying the ubiquity and pathogenic capacity of A. fumigatus is a great degree of genetic diversity observed among strains from diverse environmental and clinical sources (21–23). While many factors may contribute to the ubiquity of A. fumigatus , the production of small bioactive molecules, or secondary metabolites (SMs), has become of particular interest, as these compounds have been shown to play central roles in niche exploitation, stress tolerance, and virulence (17, 24, 25).…”

Eosinophils Are Recruited in Response to Chitin Exposure and Enhance Th2-Mediated Immune Pathology in Aspergillus fumigatus Infection

“…6A). However, the virulence of Af5517 was decreased relative to that of Af293 (45), and BALB/c mice are less susceptible to IPA than other strains (29). It will be of interest to induce Th2 responses to more virulent isolates and include more susceptible mouse strains in future studies to observe the effect of these experimental manipulations on the role of eosinophils in Th2-mediated pathology.…”

Alarmin(g) the innate immune system to invasive fungal infections

“…It is important to note that in the above mentioned studies in which discrepancies concerning IL-1 dependency arise, different A. fumigatus strains and morphotypes were used [29, 47, 49]. Interestingly, it is rapidly emerging that different strains of A. fumigatus can induce both dramatically different inflammatory responses [51, 52] and differing levels of virulence in vivo [52–54]. Interestingly, Rizzetto et al showed that the CEA10 isolate of A. fumigatus induced the greatest inflammation, which corresponded with its increased growth in immune competent mice [52].…”