ABSTRACT

CONTENTS 3.1 Introduction ................................................................................................................................. 25

3.1.1 Invasive Aspergillosis Is a Signifi cant Human Health Problem ..................................... 26 3.1.2 Innate Immune System and Invasive Aspergillosis Prevention and

Resolution ........................................................................................................................ 26 3.1.3 Application of Comparative Genomics to the Study of Aspergillus fumigatus .............. 27

3.2 Genome Sequences ..................................................................................................................... 27 3.2.1 Aspergillus fumigatus Af293 .......................................................................................... 27 3.2.2 Neosartorya fi scheri NRRL181 (Aspergillus fi scherianus) ........................................... 28 3.2.3 Aspergillus clavatus NRRL1 .......................................................................................... 28 3.2.4 Sequence Divergence, Synteny, and Chromosomal Location ........................................ 28

3.3 Virulence Genes .......................................................................................................................... 29 3.3.1 Genes Implicated in Virulence ........................................................................................ 30 3.3.2 Function of Virulence Genes .......................................................................................... 30 3.3.3 What Is Virulence? .......................................................................................................... 32

3.4 Secondary Metabolite Biosynthetic Gene Clusters .................................................................... 32 3.4.1 Clusters in Aspergillus fumigatus Af293 ........................................................................ 32 3.4.2 Associating Clusters with Products ................................................................................ 32 3.4.3 Evolution of Clusters ....................................................................................................... 34

3.5 Sex and Sex Genes ...................................................................................................................... 35 3.5.1 Mating loci in Aspergillus fumigatus, Aspergillus clavatus, and

Neosartorya fi scheri ........................................................................................................ 36 3.6 Status of Aspergillus fumigatus Genome Annotation ................................................................ 37 3.7 Summary and Prospects ............................................................................................................. 38 References ............................................................................................................................................ 38

3.1 Introduction The genus Aspergillus was named by P. A. Micheli in 1729 after a holy water sprinkler, or aspergillum, which resembled the genus-characteristic conidia-forming structure of these fungi.1 Aspergillus is an extremely diverse and widely distributed genus of fi lamentous ascomycete fungi. It includes over 200 species of mostly asexual fungi found ubiquitously in soil as well as in forage products, food, dust, organic debris, and decomposing vegetation.2 Being supreme opportunists, the aspergilli have adapted to various chemical, physical, and biological stresses and have repeatedly changed their lifestyle and reproductive mode in the course of evolution. While most of them are thought to be saprophytes, a surprising

number of species are able to infect wounded plants and animals. The advent of immunosuppressive agents and other medical advances created a new biological niche for aspergilli, the immunocompromised human host.