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Human genome-wide RNAi screen for host factors that modulate intracellular Salmonella growth.

Publication ,  Journal Article
Thornbrough, JM; Hundley, T; Valdivia, R; Worley, MJ
Published in: PLoS One
2012

Salmonella enterica is a bacterial pathogen of humans that can proliferate within epithelial cells as well as professional phagocytes of the immune system. While much has been learned about the microbial genes that influence the infectious process through decades of intensive research, relatively little is known about the host factors that affect infection. We performed a genome-wide siRNA screen to identify host genes that Salmonella enterica serovar Typhimurium (S. typhimurium) utilizes to facilitate growth within human epithelial cells. In this screen, with siRNAs targeting every predicted gene in the human genome, we identified 252 new human-host-susceptibility factors (HSFs) for S. typhimurium. We also identified 39 genes whose silencing results in increased intracellular growth of S. typhimurium. The HSFs identified are regulated most centrally by NFκB and associate with each other through an extremely dense network of interactions that center around a group of kinases. Most genes identified were not previously appreciated as playing roles in the intracellular lifecycle of S. enterica. Numerous HSFs identified with interesting characteristics that could play plausible roles in mediating intracellular microbial growth are discussed. Importantly, this study reveals significant overlap between the host network that supports S. typhimurium growth within human epithelial cells and the one that promotes the growth of Mycobacterium tuberculosis within human macrophages. In addition to providing much new information about the molecular mechanisms underlying S. enterica-host cell interplay, all 252 HSFs identified are candidates for new anti-microbial targets for controlling S. enterica infections, and some may provide broad-spectrum anti-microbial activity.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

6

Start / End Page

e38097

Location

United States

Related Subject Headings

  • Salmonella typhimurium
  • Salmonella Infections
  • RNA, Small Interfering
  • RNA Interference
  • Mycobacterium tuberculosis
  • Humans
  • Host-Pathogen Interactions
  • Host-Derived Cellular Factors
  • Genome, Human
  • General Science & Technology
 

Citation

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Thornbrough, J. M., Hundley, T., Valdivia, R., & Worley, M. J. (2012). Human genome-wide RNAi screen for host factors that modulate intracellular Salmonella growth. PLoS One, 7(6), e38097. https://doi.org/10.1371/journal.pone.0038097
Thornbrough, Joshua M., Tom Hundley, Raphael Valdivia, and Micah J. Worley. “Human genome-wide RNAi screen for host factors that modulate intracellular Salmonella growth.PLoS One 7, no. 6 (2012): e38097. https://doi.org/10.1371/journal.pone.0038097.
Thornbrough JM, Hundley T, Valdivia R, Worley MJ. Human genome-wide RNAi screen for host factors that modulate intracellular Salmonella growth. PLoS One. 2012;7(6):e38097.
Thornbrough, Joshua M., et al. “Human genome-wide RNAi screen for host factors that modulate intracellular Salmonella growth.PLoS One, vol. 7, no. 6, 2012, p. e38097. Pubmed, doi:10.1371/journal.pone.0038097.
Thornbrough JM, Hundley T, Valdivia R, Worley MJ. Human genome-wide RNAi screen for host factors that modulate intracellular Salmonella growth. PLoS One. 2012;7(6):e38097.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

6

Start / End Page

e38097

Location

United States

Related Subject Headings

  • Salmonella typhimurium
  • Salmonella Infections
  • RNA, Small Interfering
  • RNA Interference
  • Mycobacterium tuberculosis
  • Humans
  • Host-Pathogen Interactions
  • Host-Derived Cellular Factors
  • Genome, Human
  • General Science & Technology