Aspergillus fumigatus and aspergillosis - PubMed (original) (raw)

Review

Aspergillus fumigatus and aspergillosis

J P Latgé. Clin Microbiol Rev. 1999 Apr.

Abstract

Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.

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Figures

FIG. 1

Light microscopy of typical A. fumigatus sporulating structures.

FIG. 2

Schematic representation of the λ3.9 probe of A. fumigatus used for molecular studies and typical hybridization patterns obtained with _Eco_RI-digested total DNA probed with the entire _Sal_I-_Sal_I fragment (A) and _Eco_RI fragments of the repeated sequence (B to E). The repeated element _Afut_1 (squares) is an inactive retroelement of 6.9 kb bounded by two LTRs (▸) and with sequences homologous to reverse transcriptase (RT), RNase H, and endonuclease (endo) encoded by the pol genes of retrotransposons.

FIG. 3

Schematic representation of steps involved in the development of a diagnostic test for the detection of antigen in the biological fluids of patients with IA, using GM as an example.

FIG. 4

Strategies currently available to disrupt genes in A. fumigatus (A) and to create a bank of A. fumigatus mutants by using the restriction enzyme-mediated integration strategy (B). E1 and E2 are endonucleases favoring a single-copy integration of the marker in the A. fumigatus genome. wt, wild type; OMP, orotidine-5′-phosphate; 5FOA, 5-fluoroorotic acid.

FIG. 5

Effect of different immunosuppressive drugs and routes of infection on the number of conidia required to induce IA in outbred Swiss mice. Data from references , , , , , , , , , , , , , and .

FIG. 6

Role of the host innate immunity against A. fumigatus and its modulation by immunosuppressive agents used in BMT.

FIG. 7

Cytokines and their possible role in modulating cellular immunity in response to A. fumigatus in experimental murine aspergillosis.

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Aspergillus fumigatus and aspergillosis - PubMed (original) (raw)