In vitro utilization of mucin, lung polymers, plant cell walls and insect cuticle by Aspergillus fumigatus, Metarhizium anisopliae and Haematonectriahaematococca

Aspergillus fumigatus is saprotrophic with an unusual ability to colonize t he respiratory tract. The mechanisms that permit pathogenicity may have evo lved to adapt the fungus to life as a saprobe. To define the nature of thes e adaptations and identify common themes in fungal pathogenesis to vertebra tes, insects and plants, we compared A. fumigatus with a plant pathogen (Ha ematonectria haematococca) and an insect pathogen (Metarhizium anisopliae) in their abilities to degrade and utilize host-derived macromolecules (hors e lung polymers, porcine mucin, hyaluronic acid, alfalfa cell walls and coc kroach cuticle). Each fungus produced a similar range of proteases on mucin and lung polymers, and high levels of several glycosidic enzymes on mucin and plant cell walls, which contain inductive carbohydrate substrates. Foll owing 18 h of growth by A. fumigatus at pH 4 or pH 8, the degradation of mu cin carbohydrates and mucin protein were approximately 40% and 75% respecti vely, suggesting that the aspartyl proteases (produced at pH 4) and the sub tilisin proteases (produced at pH 8) are more important than carbohydrases for degrading mucin. The highly glycosylated mucin residue remaining after 18 h growth resisted further degradation, in part due to bound sialic acid as A. fumigatus secretes a sulphatase but not sialidase. Hyaluronidase acti vity (an important virulence factor in bacteria) was not produced by A. fum igatus, M. anisopliae or H. haematococca, but each fungus secreted a range of other enzymes (phospholipase A2, phospholipase C, acid phosphatase, alka li phosphatase, phosphodiesterase and esterase) that are common toxic compo nents of bacteria as well as reptilia and invertebrate venoms. Thus thermot olerant opportunists such as A. fumigatus may sustain themselves and cause disease in human hosts using depolymerases that are widely distributed in f ungi and that provide them with the versatility to exploit many environment s.