Eosinophils have been traditionally perceived as terminally differentiated cytotoxic effector cells. Recent studies have profoundly altered this simplistic view of eosinophils and their function. New ...insights into the molecular pathways that control the development, trafficking and degranulation of eosinophils have improved our understanding of the immunomodulatory functions of these cells and their roles in promoting homeostasis. Likewise, recent developments have generated a more sophisticated view of how eosinophils contribute to the pathogenesis of different diseases, including asthma and primary hypereosinophilic syndromes, and have also provided us with a more complete appreciation of the activities of these cells during parasitic infection.
Fungi can fuse with other individuals to enable cooperative growth, although this process is restricted by certain self/non-self recognition systems. A novel layer of compatibility has now been ...discovered, acting at the stage of germling cell wall fusion, showing the remarkable complexity of allorecognition in fungi.
Fungi can fuse with other individuals to enable cooperative growth, although this process is restricted by certain self/non-self recognition systems. A novel layer of compatibility has now been discovered, acting at the stage of germling cell wall fusion showing the remarkable complexity of allorecognition in fungi.
Aspergillus fumigatus is a saprotrophic fungus whose spores are ubiquitous in the atmosphere. It is also an opportunistic human pathogen in immunocompromised individuals, causing potentially lethal ...invasive infections, and is associated with severe asthma and sinusitis. The species is only known to reproduce by asexual means, but there has been accumulating evidence for recombination and gene flow from population genetic studies, genome analysis, the presence of mating-type genes and expression of sex-related genes in the fungus. Here we show that A. fumigatus possesses a fully functional sexual reproductive cycle that leads to the production of cleistothecia and ascospores, and the teleomorph Neosartorya fumigata is described. The species has a heterothallic breeding system; isolates of complementary mating types are required for sex to occur. We demonstrate increased genotypic variation resulting from recombination between mating type and DNA fingerprint markers in ascospore progeny from an Irish environmental subpopulation. The ability of A. fumigatus to engage in sexual reproduction is highly significant in understanding the biology and evolution of the species. The presence of a sexual cycle provides an invaluable tool for classical genetic analyses and will facilitate research into the genetic basis of pathogenicity and fungicide resistance in A. fumigatus, with the aim of improving methods for the control of aspergillosis. These results also yield insights into the potential for sexual reproduction in other supposedly 'asexual' fungi.
Abstract
Major insights into sexual development and cryptic sexuality within filamentous fungi have been gained from investigations using Aspergillus species. Here, an overview is first given into ...sexual morphogenesis in the aspergilli, describing the different types of sexual structures formed and how their production is influenced by a variety of environmental and nutritional factors. It is argued that the formation of cleistothecia and accessory tissues, such as Hülle cells and sclerotia, should be viewed as two independent but co-ordinated developmental pathways. Next, a comprehensive survey of over 75 genes associated with sexual reproduction in the aspergilli is presented, including genes relating to mating and the development of cleistothecia, sclerotia and ascospores. Most of these genes have been identified from studies involving the homothallic Aspergillus nidulans, but an increasing number of studies have now in addition characterized ‘sex-related’ genes from the heterothallic species Aspergillus fumigatus and Aspergillus flavus. A schematic developmental genetic network is proposed showing the inter-relatedness between these genes. Finally, the discovery of sexual reproduction in certain Aspergillus species that were formerly considered to be strictly asexual is reviewed, and the importance of these findings for cryptic sexuality in the aspergilli as a whole is discussed.
Sexual reproduction in the filamentous fungal genus Aspergillus is reviewed, with detailed descriptions of a series of over 75 genes known to be associated with sexual morphogenesis and a new schematic developmental network presented, together with discussion of the recent discoveries of cryptic sexuality in certain aspergilli.
A novel lichen species occurring on rocks was collected from three different localities within Deosai National Park, Gilgit-Baltistan, Pakistan. Phylogenetic analyses of the nrDNA ITS and nuLSU ...regions revealed that it clustered within the genus Anamylopsora. Further chemical and morpho-anatomical analyses confirmed its uniqueness, and it is described here as a new species under the name A. pakistanica. The distinguishing characters are: an irregularly squamulose appressed thallus on rocks without rhizines; an epinecral layer up to 25 μm thick; ascospores that are hyaline, simple, thick-walled with a smooth surface; septate paraphyses with a pigmented apical cell in a gel-like matrix; globose to subglobose pycnidia with hyaline and bacilliform pycnidiospores. In particular, the species is distinguished from other members of the genus by morpho-anatomical features including the coloration of the thalli, the presence of a thick lower cortex (up to 100 μm), and the presence of simple, thick-walled ascospores. Specimens were found at altitudes up to 4587 m, the highest elevation yet reported for Anamylopsora. A key and comparison to all existing species of the genus Anamylopsora is also given.
Sexual reproduction involving meiosis is essential in most eukaryotes. This produces offspring with novel genotypes, both by segregation of parental chromosomes as well as crossovers between ...homologous chromosomes. A sexual cycle for the opportunistic human pathogenic fungus Aspergillus fumigatus is known, but the genetic consequences of meiosis have remained unknown. Among other Aspergilli, it is known that A. flavus has a moderately high recombination rate with an average of 4.2 crossovers per chromosome pair, whereas A. nidulans has in contrast a higher rate with 9.3 crossovers per chromosome pair. Here, we show in a cross between A. fumigatus strains that they produce an average of 29.9 crossovers per chromosome pair and large variation in total map length across additional strain crosses. This rate of crossovers per chromosome is more than twice that seen for any known organism, which we discuss in relation to other genetic model systems. We validate this high rate of crossovers through mapping of resistance to the laboratory antifungal acriflavine by using standing variation in an undescribed ABC efflux transporter. We then demonstrate that this rate of crossovers is sufficient to produce one of the common multidrug resistant haplotypes found in the cyp51A gene (TR34/L98H) in crosses among parents harboring either of 2 nearby genetic variants, possibly explaining the early spread of such haplotypes. Our results suggest that genomic studies in this species should reassess common assumptions about linkage between genetic regions. The finding of an unparalleled crossover rate in A. fumigatus provides opportunities to understand why these rates are not generally higher in other eukaryotes.
Penicillium chrysogenum is a filamentous fungus of major medical and historical importance, being the original and present-day industrial source of the antibiotic penicillin. The species has been ...considered asexual for more than 100 y, and despite concerted efforts, it has not been possible to induce sexual reproduction, which has prevented sexual crosses being used for strain improvement. However, using knowledge of mating-type (MAT) gene organization, we now describe conditions under which a sexual cycle can be induced leading to production of meiotic ascospores. Evidence of recombination was obtained using both molecular and phenotypic markers. The identified heterothallic sexual cycle was used for strain development purposes, generating offspring with novel combinations of traits relevant to penicillin production. Furthermore, the MAT1-1–1 mating-type gene, known primarily for a role in governing sexual identity, was also found to control transcription of a wide range of genes with biotechnological relevance including those regulating penicillin production, hyphal morphology, and conidial formation. These discoveries of a sexual cycle and MAT gene function are likely to be of broad relevance for manipulation of other asexual fungi of economic importance.
Populations of genetically uniform microorganisms exhibit phenotypic heterogeneity, where individual cells have varying phenotypes. Such phenotypes include fitness‐determining traits. Phenotypic ...heterogeneity has been linked to increased population‐level fitness in laboratory studies, but its adaptive significance for wild microorganisms in the natural environment is unknown. Here, we addressed this by testing heterogeneity in yeast isolates from diverse environmental sites, each polluted with a different principal contaminant, as well as from corresponding control locations. We found that cell‐to‐cell heterogeneity (in resistance to the appropriate principal pollutant) was prevalent in the wild yeast isolates. Moreover, isolates with the highest heterogeneity were consistently observed in the polluted environments, indicating that heterogeneity is positively related to survival in adverse conditions in the wild. This relationship with survival was stronger than for the property of mean resistance (IC₅₀) of an isolate. Therefore, heterogeneity could be the major determinant of microbial survival in adverse conditions. Indeed, growth assays indicated that isolates with high heterogeneities had a significant competitive advantage during stress. Analysis of yeasts after cultivation for ≥ 500 generations additionally showed that high heterogeneity evolved as a heritable trait during stress. The results showed that environmental stress selects for wild microorganisms with high levels of phenotypic heterogeneity.
Aspergillus fumigatus is a medically important opportunistic pathogen and a major cause of respiratory allergy
1. The species has long been considered an asexual organism. However, genome analysis ...has revealed the presence of genes associated with sexual reproduction, including a
MAT-2 high-mobility group mating-type gene and genes for pheromone production and detection (Galagan et al., personal communication; Nierman et al., personal communication;
2, 3). We now demonstrate that
A. fumigatus has other key characteristics of a sexual species. We reveal the existence of isolates containing a complementary
MAT-1 α box mating-type gene and show that the
MAT locus has an idiomorph structure characteristic of heterothallic (obligate sexual outbreeding) fungi
4, 5. Analysis of 290 worldwide clinical and environmental isolates with a multiplex-PCR assay revealed the presence of
MAT1-1 and
MAT1-2 genotypes in similar proportions (43% and 57%, respectively). Further population genetic analyses provided evidence of recombination across a global sampling and within North American and European subpopulations. We also show that mating-type, pheromone-precursor, and pheromone-receptor genes are expressed during mycelial growth. These results indicate that
A. fumigatus has a recent evolutionary history of sexual recombination and might have the potential for sexual reproduction. The possible presence of a sexual cycle is highly significant for the population biology and disease management of the species.
Microsatellite markers can provide valuable information about gene flow and population history. We developed and tested new microsatellites for the nitrophilic lichenized fungus Xanthoria parietina ...and studied its genetic diversity and structure within the urban area of Munich, Bavaria. We compared its local genetic pattern with that of its photobiont partner Trebouxia decolorans, for which existing microsatellites were applied. For comparison, a reference site with clean air was included in the sampling. We found support for three genetic clusters in the fungus X. parietina, which occurred intermingled in collecting sites. There was a high degree of admixture within fungal populations and individuals, and analysis of molecular variance revealed a lack of population structure in the mycobiont. The Trebouxia photobiont, in contrast, exhibited structured populations which grouped into two to five genetic clusters, and individuals showed less admixture than in the mycobiont. This indicates that the two lichen partners differ in their ability to move around in the landscape. The microsatellite markers we report are polymorphic and are suitable for population genetic studies.
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