Abstract
ABSTRACTThe given strain of Aspergillus fumigatus under study varies across laboratories, ranging from a few widely used “standards,” e.g., Af293 or CEA10, to locally acquired isolates that may be unique to one investigator. Since experiments concerning physiology or gene function are seldom replicated by others, i.e., in a different A. fumigatus background, the extent to which behavioral heterogeneity exists within the species is poorly understood. As a proxy for assessing such intraspecies variability, we analyzed the light response of 15 A. fumigatus isolates and observed striking quantitative and qualitative heterogeneity among them. The majority of the isolates fell into one of two seemingly mutually exclusive groups: (i) “photopigmenters” that robustly accumulate hyphal melanin in the light and (ii) “photoconidiators” that induce sporulation in the light. These two distinct responses were both governed by the same upstream blue light receptor, LreA, indicating that a specific protein’s contribution can vary in a strain-dependent manner. Indeed, while LreA played no apparent role in regulating cell wall homeostasis in strain Af293, it was essential in that regard in strain CEA10. The manifest heterogeneity in the photoresponses led us to compare the virulence levels of selected isolates in a murine model; remarkably, the virulence did vary greatly, although not in a manner that correlated with their overt light response. Taken together, these data highlight the extent to which isolates of A. fumigatus can vary, with respect to both broad physiological characteristics (e.g., virulence and photoresponse) and specific protein functionality (e.g., LreA-dependent phenotypes).
Highlights
The given strain of Aspergillus fumigatus under study varies across laboratories, ranging from a few widely used “standards,” e.g., Af293 or CEA10, to locally acquired isolates that may be unique to one investigator
In strain Af293, a ⌬veA mutant displays increased conidiation levels, to the reports in A. nidulans [22]; in contrast, conidiation is reduced when veA is deleted in another common A. fumigatus laboratory isolate, CEA10 [23]
We predicted (i) that the genomic differences that exist between A. fumigatus strains Af293 and CEA10 reflect a greater heterogeneity within the species and (ii) that, as a result of this heterogeneity, the behavioral responses of different isolates to a common environmental stimulus would vary
Summary
The given strain of Aspergillus fumigatus under study varies across laboratories, ranging from a few widely used “standards,” e.g., Af293 or CEA10, to locally acquired isolates that may be unique to one investigator. The manifest heterogeneity in the photoresponses led us to compare the virulence levels of selected isolates in a murine model; remarkably, the virulence did vary greatly, not in a manner that correlated with their overt light response Taken together, these data highlight the extent to which isolates of A. fumigatus can vary, with respect to both broad physiological characteristics (e.g., virulence and photoresponse) and specific protein functionality (e.g., LreA-dependent phenotypes). The ascomycete mold Aspergillus nidulans has served as a premier model for understanding how fungi integrate multiple photosensory inputs In this organism, for example, asexual development (conidiation) is additively induced by blue and red light through the action of discrete photoreceptor proteins LreA and FphA, respectively [8, 9]. This induction is currently modeled to occur in two ways: in the nucleus, light-activated FphA interacts with and promotes the activity of GcnE to promote histone acetylation and induction of target loci [11]; in the cytoplasm, dark-state FphA represses the conidiation-inducing activity of the mitogen-activated protein (MAP) kinase SakA (HogA) [14]
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