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      Discovery of a sexual cycle in the opportunistic fungal pathogen Aspergillus fumigatus

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      Nature
      Springer Science and Business Media LLC

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          Abstract

          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.

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          Most cited references36

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          CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice

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            Aspergillosis case-fatality rate: systematic review of the literature.

            To update the case-fatality rate (CFR) associated with invasive aspergillosis according to underlying conditions, site of infection, and antifungal therapy, data were systematically reviewed and pooled from clinical trials, cohort or case-control studies, and case series of >/=10 patients with definite or probable aspergillosis. Subjects were 1941 patients described in studies published after 1995 that provided sufficient outcome data; cases included were identified by MEDLINE and EMBASE searches. The main outcome measure was the CFR. Fifty of 222 studies met the inclusion criteria. The overall CFR was 58%, and the CFR was highest for bone marrow transplant recipients (86.7%) and for patients with central nervous system or disseminated aspergillosis (88.1%). Amphotericin B deoxycholate and lipid formulations of amphotericin B failed to prevent death in one-half to two-thirds of patients. Mortality is high despite improvements in diagnosis and despite the advent of newer formulations of amphotericin B. Underlying patient conditions and the site of infection remain important prognostic factors.
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              The pathobiology of Aspergillus fumigatus.

              Aspergillus fumigatus is the most prevalent airborne fungal pathogen in developed countries, and in immunocompromised patients causes a usually fatal invasive aspergillosis (IA). Understanding the pathobiology of this fungal species requires not only analysis of the putative fungal virulence factors that stimulate fungal growth and/or survival in the lung environment, but also knowledge of the immune factors containing A. fumigatus in the immunocompetent host that can be debilitated by immunosuppressive therapies, triggering IA. Although the incidence of IA has dramatically increased in recent years, progress in these areas has been limited and, as yet, a single, true virulence factor has not been identified and the mechanisms responsible for protective immunity against A. fumigatus have yet to be elucidated.
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                Author and article information

                Journal
                Nature
                Nature
                Springer Science and Business Media LLC
                0028-0836
                1476-4687
                January 2009
                January 22 2009
                January 2009
                : 457
                : 7228
                : 471-474
                Article
                10.1038/nature07528
                19043401
                b87005d4-9765-4356-814f-676945b5f107
                © 2009

                http://www.springer.com/tdm

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