Genetic and virulence variation in an environmental population of the opportunistic pathogen Aspergillus fumigatus

Abstract

Environmental populations of the opportunistic pathogen Aspergillus fumigatus have been shown to be genotypically diverse and to contain a range of isolates with varying pathogenic potential. In this study, we combined two RAPD primers to investigate the genetic diversity of environmental isolates from Manchester collected monthly over 1 year alongside Dublin environmental isolates and clinical isolates from patients. RAPD analysis revealed a diverse genotype, but with three major clinical isolate clusters. When the pathogenicity of clinical and Dublin isolates was compared with a random selection of Manchester isolates in a Galleria mellonella larvae model, as a group, clinical isolates were significantly more pathogenic than environmental isolates. Moreover, when relative pathogenicity of individual isolates was compared, clinical isolates were the most pathogenic, Dublin isolates were the least pathogenic and Manchester isolates showed a range in pathogenicity. Overall, this suggests that the environmental population is genetically diverse, displaying a range in pathogenicity, and that the most pathogenic strains from the environment are selected during patient infection. INTRODUCTIONAspergillus fumigatus is an opportunistic fungal pathogen that can cause aspergillosis in immunocompromised patients, such as those with neutropenia or on immunosuppressive therapy following solid organ transplantation (Abad et al., 2010;Ben-Ami et al., 2010;Dagenais & Keller, 2009;Latgé, 1999;Rementeria et al., 2005). The principal route of infection is through the inhalation of airborne spores, which due to their small spore size are able to reach the alveoli (Dagenais & Keller, 2009;Ibrahim-Granet et al., 2003;Latgé, 1999;O'Gorman, 2011;Philippe et al., 2003). While other aspergilli can cause opportunistic infections (such as Aspergillus terreus and Aspergillus flavus), A. fumigatus accounts for~90 % of all cases despite airborne spore numbers only accounting for ,1 % of all Aspergillus spores (Rementeria et al., 2005). A number of studies have shown a high degree of genetic variation within the A. fumigatus population, and whilst some studies have indicated potential geographical subgroups, comparisons between clinical isolates and environmental isolates have largely been unable to distinguish these populations (Araujo et al., 2010;Aufauvre-Brown et al., 1992;Balajee et al., 2008;Chazalet et al., 1998;Denning et al., 1990;Duarte-Escalante et al., 2009; Leenders et al., 1999;Menotti et al., 2005). Moreover, epidemiological studies have largely failed to match genotypes in infected patients with genotypes found in hospitals, in part due to the high level of genetic diversity in the environmental populations (Araujo et al., 2010;Bart-Delabesse et al., 1999;Chazalet et al., 1998;Guinea et al., 2011; Leenders et al., 1999;de Valk et al., 2007), and similar findings have been reported in avian populations (Arné et al., 2011;Lair-Fulleringer et al., 2003;Olias et al., 2011). Whilst genotyping of isolates from some individual patient...

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

“…Analysis of SNPs among all publicly available sequenced isolates (>100 total; 95 unique isolates included in the present study) across a global range of clinical and environmental sources shows considerable genetic diversity, consistent with previous reports of genetic variance in A. fumigatus (22). Given that we are unable to know how, when, and where ISSFT-021 and IF1SW-F4 initially colonized the ISS, it is curious that both strains bare the closest relationship to the strains Af300 and JN10 (27) (Fig.…”

“…While a detailed analysis of specific SNPs in the ISS isolates was beyond the scope of our present study, the number total SNP differences of ISSFT-021 and IF1SW-F4 compared to Af293 were within the range of documented variance among existing sequences of environmental A. fumigatus strains (Fig. 1), suggesting that, without a more detailed analysis, the ISS strains likely reflect genetic diversity already found on Earth (22). …”

“…Interestingly, studies have been unable to consistently support the hypothesis that clinical strains have undergone a selective bottleneck and are therefore more virulent than environmental isolates (21, 22, 53). As both ISSFT-021 and IF1SW-F4 are environmental isolates, albeit from a highly unusual environment, our finding that both ISS strains are more virulent than the two clinical strains reinforces the idea that isolation source is not predictive of pathogenic potential and also reinforces the conclusion that all strains of A. fumigatus , regardless of origin, possess an infective potential (54).…”

“…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).…”

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].…”