Histoplasma capsulatumutilizes siderophores for intracellular iron acquisition in macrophages

• DOI: 10.3109/13693786.2011.558930
• Publication Date: 2011-02-22T15:12:38Z
• Authors: Jeremy Hilty; A. George Smulian; Simon L. Newman
• Keywords: Histoplasma; Dimorphic fungus; Intracellular parasite

Histoplasma capsulatum is a dimorphic fungal pathogen that survives and replicates within macrophages (Mφ). Studies in human murine Mφ demonstrate the intracellular growth of H. yeasts exquisitely sensitive to availability iron. As produces hydroxamate siderophores, we sought determine if siderophores were required for survival Mφ, model pulmonary histoplasmosis. The expression SID1 (coding L-ornithine-N5-monooxygenase) was silenced by RNA interference (RNAi) strain G217B, abolished gene targeting G186AR. G217B SID1-silenced grew normally rich medium, did not synthesize unable grow on apotransferrin-chelated medium. Their significantly decreased compared wild type (WT) yeasts, but restored WT levels addition exogenous iron, or restoration expression. Similar results obtained with G186AR Δsid1 yeasts. Compared demonstrated C57BL/6 mice reduced lungs spleens seven days after infection, 40% given lethal inoculum survived. These experiments that: (1) siderophore biosynthesis (2) optimum (3) inhibition vivo reduces virulence