Cutaneous model of invasive aspergillosis.
Cutaneous models have proven useful in studies of the pathogenesis and treatment of Gram-positive bacterial infections. Because cutaneous invasive aspergillosis (IA) occurs in the clinical setting, we sought to develop a nonlethal murine cutaneous model of IA. We induced cutaneous IA in cyclophosphamide-treated nude BALB/c mice by subcutaneous injection of Aspergillus fumigatus conidia. Skin lesion areas correlated well with tissue fungal burdens, allowing dynamic visual monitoring of cutaneous infections. The cutaneous model accurately reflected alterations in A. fumigatus pathogenicity resulting from deletions of recognized virulence genes (pabaA, sidA, and pksP). Moreover, analysis of the roles of conidial and mycelial catalases revealed that the former is required for the initiation of cutaneous aspergillosis, whereas the latter contributes to its propagation. Finally, posaconazole treatment reduced skin lesion areas relative to those of untreated and fluconazole-treated controls. This novel cutaneous model system should be applicable to comparative studies of the pathogenesis, treatment, and tissue specificity of IA.
Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
Ronen
R
Ben-Ami
Russell E
RE
Lewis
Konstantinos
K
Leventakos
Jean-Paul
JP
Latgé
Dimitrios P
DP
Kontoyiannis
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D002374:Catalase / Q000235:genetics; D003520:Cyclophosphamide / Q000494:pharmacology; D003881:Dermatomycoses / Q000188:drug therapy; D004195:Disease Models, Animal; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D025301:Hyphae / Q000187:drug effects / Q000378:metabolism; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008351:Mannans / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016296:Mutagenesis; D012867:Skin / Q000378:metabolism / Q000382:microbiology; D013170:Spores / Q000187:drug effects / Q000235:genetics; D014230:Triazoles / Q000494:pharmacology*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D008351:Mannans; D014230:Triazoles; D037521:Virulence Factors; C012990:galactomannan; C101425:posaconazole; D003520:Cyclophosphamide; D002374:Catalase; D005690:Galactose