Intracellular Parasitism by Histoplasma capsulatum: Fungal Virulence and Calcium Dependence

• Published in: Science (American Association for the Advancement of Science) Vol. 290; no. 5495; pp. 1368 - 1372
• Main Authors: Sebghati, Tricia Schurtz, Engle, Jacquelyn T., Goldman, William E.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 17.11.2000; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Alleles; Animals; Biological and medical sciences; Calcium; Calcium - metabolism; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; CBP1 gene; Cell Line; Cell Survival; Coding; DNA probes; Environment; Fundamental and applied biological sciences. Psychology; Fungi; Fungi, Pathogenic; Gene Targeting; Genes, Fungal; Genetic Complementation Test; Genetics; Histoplasma; Histoplasma - genetics; Histoplasma - growth & development; Histoplasma - metabolism; Histoplasma - pathogenicity; Histoplasma capsulatum; Histoplasmosis; Histoplasmosis - microbiology; Immunosuppression; Infections; Lung Diseases, Fungal - microbiology; Lungs; Macrophages; Macrophages - microbiology; Methods; Mice; Microbiology; Mutagenesis; Mycology; Parasites; Pathogenic fungi; Pathogenicity, host-agent relations, miscellaneous strains, epidemiology; Phenotype; Plasmids; Polymerase chain reaction; Proteins; Recombination, Genetic; Risk factors; Transformation, Genetic; Virulence; Yeasts; United States; Animal model; Yeast; Calcium; Mycosis; Calcium binding protein 1; Rodentia; Histoplasma capsulatum; Host agent relation; In vitro; Survival; Fungi; Infection; Pathogenicity; In vivo; Binding protein; Vertebrata; Mammalia; Mouse; Fungi Imperfecti; Infected cell; Intracellular; Thallophyta; Macrophage
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.290.5495.1368

Histoplasma capsulatum is an effective intracellular parasite of macrophages and causes the most prevalent fungal respiratory disease in the United States. A "dimorphic" fungus, H. capsulatum exists as a saprophytic mold in soil and converts to the parasitic yeast form after inhalation. Only the yeasts secrete a calcium-binding protein (CBP) and can grow in calcium-limiting conditions. To probe the relation between calcium limitation and intracellular parasitism, we designed a strategy to disrupt CBP1 in H. capsulatum using a telomeric linear plasmid and a two-step genetic selection. The resulting cbp1 yeasts no longer grew when deprived of calcium, and they were also unable to destroy macrophages in vitro or proliferate in a mouse model of pulmonary infection.