Publication Date:
2000-11-18
Description:
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 resultingcbp1 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sebghati, T S -- Engle, J T -- Goldman, W E -- A107172/PHS HHS/ -- AI25584/AI/NIAID NIH HHS/ -- HL07317/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2000 Nov 17;290(5495):1368-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology, Campus Box 8230, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11082066" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Animals
;
Calcium/*metabolism
;
Calcium-Binding Proteins/*genetics/*metabolism
;
Cell Line
;
Cell Survival
;
Gene Targeting
;
Genes, Fungal
;
Genetic Complementation Test
;
Histoplasma/genetics/growth & development/metabolism/*pathogenicity
;
Histoplasmosis/*microbiology
;
Lung Diseases, Fungal/microbiology
;
Macrophages/*microbiology
;
Mice
;
Mutagenesis
;
Phenotype
;
Plasmids
;
Recombination, Genetic
;
Transformation, Genetic
;
Virulence
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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