Aspergillus terreus Accessory Conidia Are Unique in Surface Architecture, Cell Wall Composition and Germination Kinetics

Abstract

Infection with Aspergillus terreus is more likely to result in invasive, disseminated disease when compared to other Aspergillus species; importantly this species appears to be less susceptible to the antifungal drug amphotericin B. Unique to this species is the ability to produce specialized structures denoted as accessory conidia (AC) directly on hyphae both in vitro and in vivo. With the hypothesis that production of AC by A. terreus may enhance virulence of this organism, we analyzed the phenotype, structure and metabolic potential of these conidia. Comparison of A. terreus phialidic conidia (conidia that arise from conidiophores, PC) and AC architecture by electron microscopy revealed distinct morphological differences between the two conidial forms; AC have a smoother, thicker outer cell surface with no apparent pigment-like layer. Further, AC germinated rapidly, had enhanced adherence to microspheres, and were metabolically more active compared to PC. Additionally, AC contained less cell membrane ergosterol, which correlated with decreased susceptibility to AMB as determined using a flow cytometry based analysis. Furthermore, AC exhibited surface patches of β1-3 glucan, suggestive of attachment scarring. Collectively, the findings of this study suggest a possible role for AC in A. terreus pathogenesis.

Aspergillus terreusaccessory conidia are multinucleated, hyperpolarizing structures that display differential dectin staining and can induce heightened inflammatory responses in a pulmonary model of aspergillosis

“…22 Similarly, the asexual conidia of A. fumigatus and A. terreus are distinct in color and cell size and recent studies in our laboratory indicate differential rates of germination and hydrophobicity between these conidia. 1 In this study, we further demonstrate that A. terreus PC have an average of two nuclei compared to A. fumigatus conidia, which often contains one nucleus. Additionally, PC of both species exhibit distinct cell surface characteristics including β-glucan expression.…”

“…Given the differences observed in A. terreus PC and AC β-glucan labeling in our previous study, 1 we were also interested in looking at stage specific β-glucan display between these conidial forms. We therefore examined the ability of dectin-1 to recognize A. terreus AC at different stages of maturation (Fig.…”

“…1 Accessory conidia are produced both in vitro and in vivo, and a recent study from our laboratory indicated that AC were morphologically distinct from PC in that they lacked a pigment-like outer layer and were larger than PC. 1 We demonstrated other phenotypic differences between these two conidial forms including the ability of AC to germinate more rapidly, enhanced adherence of AC to microspheres, heightened AC metabolic activity, less cell membrane ergosterol and lower susceptibility of AC to the antifungal drug amphotericin B. 1,27 Additionally, our study showed that dormant AC displayed uniform β-glucan staining, with enhanced staining in a ring pattern suggestive of a bud scar, in contrast to PC, for…”

New Insight into Amphotericin B Resistance in Aspergillus terreus

“…Membrane damage increased membrane permeability and intracellular oxidative damage, thought to be responsible for AMB action (14,19). Reduced susceptibility to AMB has been associated with the upregulation of several ergosterol biosynthesis genes (ERG5, ERG6, and ERG25) and decreased ergosterol content in the fungal cell membrane (35)(36)(37). In contrast, our data suggest that the ergosterol content does not play a major role in AMB resistance in the A. terreus strains we tested.…”

The duality ofAspergillus terreus: Differential immune responses to distinct conidia

“…Species within Aspergillus, including Aspergillus terreus, produce asexual conidia that arise from conidiophores (phialidic conidia, PC). 32 These PC are produced by Aspergillus spp in the natural environment and on laboratory media but are rarely produced during in vivo infection. In addition to PC, Aspergillus terreus produces another type of asexual conidia denoted as accessory conidia (AC), which arise directly on hyphae 32 ( Fig.…”