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Title: A Coccidioides posadasii CPS1 deletion mutant is avirulent and protects mice from lethal infection      
keywords:
Transcriptome or Gene expression
ID:
PRJNA338286
description:
The CPS1 gene was identified as a virulence factor in the maize pathogen, Cochliobolus heterostrophus. Hypothesizing that the homologous gene in Coccidioides posadasii (Cp) could be important for virulence, we created a deletion mutant, Δcps1, which was unable to cause disease in three strains of mice (C57BL/6, BALB/c, or the severely immunodeficient NOD-scid,γcnull [NSG]). Only a single colony was recovered from one of 60 C57BL/6 mice following intranasal infections of up to 4400 spores. Following administration of very high doses (10,000 to 2.5 x 10^7 spores) to NSG and BALB/c mice, spherules were observed in lung sections at time points from day 3 to day 10 post-infection, but nearly all appeared degraded with infrequent endosporulation. Although the role of CPS1 in virulence is not understood, phenotypic alterations and transcription differences of at least 33 genes in Δcps1 vs. Cp is consistent with both metabolic and regulatory functions for the gene. The in vitro phenotype of Δcps1 showed slower growth of mycelia with delayed and lower spore production compared to Cp, and in vitro spherules were smaller. Vaccination of C57BL/6 or BALB/c mice with live Δcps1 spores either intranasally, intraperitoneally or subcutaneously resulted in over 95% survival with mean residual lung fungal burdens <1000 colony-forming units from an otherwise lethal Cp intranasal infection. Considering its apparently complete attenuation of virulence and the high degree of resistance to Cp infection when used as a vaccine, Δcps1 is a promising vaccine candidate for preventing coccidioidomycosis in humans or other animals. Overall design: Wild type and CPS1 deletion mutant strains of Coccidioides posadasii strain Silveira spherules grown for 48 hours in Converse medium at 38 degrees celsius in duplicate. RNAseq was performed on an Illumina HiSeq2000 (2x100 paired end).
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA338286
authentication:
none
authorization:
none
ID:
pmid:27481239
name:
Coccidioides posadasii
ncbiID:
ncbitax:199306
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject