Transcriptome analysis of Cryptosporidium parvum development in vitro.
cryptosporidiosis is caused primarily by two Cryptosporidium species, C. parvum and C.
hominis. The infection is frequent in immune-compromised individuals and considered an
opportunistic infection. Effective drugs to control cryptosporidiosis do not exist.
Cryptosporidium parasites are cultured in monolayers of epithelial cells but the method
is deficient because the parasite... read morecannot be continuously propagated. Drug screening
efforts are hampered by a lack of culture methods enabling the continuous propagation of
the parasite. By comparing gene expression in infected and uninfected cultured cell
monolayers we identified genes that are involved in apoptosis, cell growth and division
are differentially expressed in infected cells. In addition to the potential for
improving Cryptosporidium culture and facilitating drug screening in culture, sequencing
the transcriptome of infected cells in high-throughput (RNA-Seq) provides new insights
into the intracellular development of Cryptosporidium parasites. By making
high-throughput sequence data from the transcriptome of infected cell cultures
(intercellular stages of the parasite) available to the research community, new
opportunities for investigating the biology of those stages of the infection, which
cause disease and have remained virtually unexplored, were created. This study found a
total of 696 genes to be differentially expressed (False Discovery Rate <0.05). Based
on differentially expressed genes, host metabolic pathways were identified as
differentially expressed in response to C. parvum infection. Some of these
transcriptional changes have been studied before. The findings of this current study
found up-regulation of host heat-shock genes and genes for Cysteine X Cysteine (CXC)
chemokine. Host genes involved in cell proliferation and apoptosis found to be
differentially expressed. In conclusion this study illustrated significant changes in
host biological functions as a result of C. parvum infection and provides new
understandings into biology of infectious disease caused by this intracellular protozoan
Thesis (M.S.)--Tufts University, 2016.
Submitted to the Dept. of Clinical & Translational Science.
Advisor: Giovanni Widmer.
Committee: Farzad Noubary, and Gordon Huggins.
Keyword: Molecular biology.read less