NDLI: Characterization of Intracellular Growth Regulator icgR by Utilizing Transcriptomics To Identify Mediators of Pathogenesis in Shigella flexneri

Content Provider	PubMed Central
Author	Morris, Carolyn R. Grassel, Christen L. Redman, Julia C. Sahl, Jason W. Barry, Eileen M. Rasko, David A.
Editor	Payne, S. M.
Copyright Year	2013
Abstract	Shigella species Gram-negative bacteria which cause a diarrheal disease, known as shigellosis, by invading and destroying the colonic mucosa and inducing a robust inflammatory response. With no vaccine available, shigellosis annually kills over 600,000 children in developing countries. This study demonstrates the utility of combining high-throughput bioinformatic methods with in vitro and in vivo assays to provide new insights into pathogenesis. Comparisons of in vivo and in vitro gene expression identified genes associated with intracellular growth. Additional bioinformatics analyses identified genes that are present in S. flexneri isolates but not in the three other Shigella species. Comparison of these two analyses revealed nine genes that are differentially expressed during invasion and that are specific to S. flexneri. One gene, a DeoR family transcriptional regulator with decreased expression during invasion, was further characterized and is now designated icgR, for intracellular growth regulator. Deletion of icgR caused no difference in growth in vitro but resulted in increased intracellular replication in HCT-8 cells. Further in vitro and in vivo studies using high-throughput sequencing of RNA transcripts (RNA-seq) of an isogenic ΔicgR mutant identified 34 genes that were upregulated under both growth conditions. This combined informatics and functional approach has allowed the characterization of a gene and pathway previously unknown in Shigella pathogenesis and provides a framework for further identification of novel virulence factors and regulatory pathways.
Related Links	http://dx.doi.org/10.1128/iai.00537-13
Ending Page	3076
Page Count	9
Starting Page	3068
File Format	PDF
ISSN	00199567
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	9
Volume Number	81
Language	English
Publisher	American Society for Microbiology
Publisher Date	2013-09-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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Analysis of the Proteome of Intracellular Shigella flexneri Reveals Pathways Important for Intracellular Growth

Expression of aerobactin genes by Shigella flexneri during extracellular and intracellular growth.

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Characterization of Intracellular Growth Regulator icgR by Utilizing Transcriptomics To Identify Mediators of Pathogenesis in Shigella flexneri

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Analysis of the Proteome of Intracellular Shigella flexneri Reveals Pathways Important for Intracellular Growth

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