Histoplasma Requires SID1, a Member of an Iron-Regulated Siderophore Gene Cluster, for Host Colonization

• DOI: 10.1371/journal.ppat.1000044
• Publication Date: 2008-04-10T21:40:19Z
• Authors: Lena H. Hwang; Jacob A. Mayfield; Jasper Rine; Anita Sil
• Keywords: Gene cluster

The macrophage is the primary host cell for fungal pathogen Histoplasma capsulatum during mammalian infections, yet little known about genes required intracellular replication in host. Since ability to scavenge iron from important virulence of most pathogens, we investigated role acquisition H. pathogenesis. acquires through action ferric reductases and production siderophores, but responsible these activities their have not been determined. We identified a discrete set co-regulated whose transcription induced under low conditions. These all appeared be involved synthesis, secretion, utilization siderophores. Surprisingly, majority transcriptionally were found clustered adjacent each other genome three sequenced strains capsulatum, suggesting that proximity might foster coordinate gene regulation. Additionally, consensus sequence promoters may contribute iron-regulated expression. included L-ornithine monooxygenase (SID1), enzyme catalyzes first committed step siderophore fungi. Disruption SID1 by allelic replacement resulted poor growth conditions, as well loss production. Strains deficient showed significant defect murine bone-marrow-derived macrophages attenuation mouse model infection. data indicated utilizes siderophores addition mechanisms optimal