Shigella flexneri infection in Caenorhabditis elegans

Cytopathological examination and identification of host responses

Divya T. George, Carolyn A. Behm, David H. Hall, Ulrike Mathesius, Melanie Rug, Ken C.Q. Nguyen, Naresh K. Verma

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The Gram-negative bacterium Shigella flexneri is the causative agent of shigellosis, a diarrhoeal disease also known as bacillary dysentery. S. flexneri infects the colonic and rectal epithelia of its primate host and induces a cascade of inflammatory responses that culminates in the destruction of the host intestinal lining. Molecular characterization of host-pathogen interactions in this infection has been challenging due to the host specificity of S. flexneri strains, as it strictly infects humans and non-human primates. Recent studies have shown that S. flexneri infects the soil dwelling nematode Caenorhabditis elegans, however, the interactions between S. flexneri and C. elegans at the cellular level and the cause of nematode death are unknown. Here we attempt to gain insight into the complex host-pathogen interactions between S. flexneri and C. elegans. Using transmission electron microscopy, we show that live S. flexneri cells accumulate in the nematode intestinal lumen, produce outer membrane vesicles and invade nematode intestinal cells. Using two-dimensional differential in-gel electrophoresis we identified host proteins that are differentially expressed in response to S. flexneri infection. Four of the identified genes, aco-1, cct-2, daf-19 and hsp-60, were knocked down using RNAi and ACO-1, CCT-2 and DAF-19, which were identified as up-regulated in response to S. flexneri infection, were found to be involved in the infection process. aco-1 RNAi worms were more resistant to S. flexneri infection, suggesting S. flexneri-mediated disruption of host iron homeostasis. cct-2 and daf-19 RNAi worms were more susceptible to infection, suggesting that these genes are induced as a protective mechanism by C. elegans. These observations further our understanding of the processes involved in S. flexneri infection of C. elegans, which is immensely beneficial to the routine use of this new in vivo model to study S. flexneri pathogenesis.

Original languageEnglish (US)
Article numbere106085
JournalPLoS One
Volume9
Issue number9
DOIs
StatePublished - Sep 4 2014

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Shigella flexneri
Caenorhabditis elegans
Pathogens
Genes
Infection
Electrophoresis
Linings
infection
Bacteria
Iron
Gels
Transmission electron microscopy
Membranes
Soils
RNA Interference
Nematoda
Bacillary Dysentery
Host-Pathogen Interactions
Proteins
host-pathogen relationships

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Shigella flexneri infection in Caenorhabditis elegans : Cytopathological examination and identification of host responses. / George, Divya T.; Behm, Carolyn A.; Hall, David H.; Mathesius, Ulrike; Rug, Melanie; Nguyen, Ken C.Q.; Verma, Naresh K.

In: PLoS One, Vol. 9, No. 9, e106085, 04.09.2014.

Research output: Contribution to journalArticle

George, Divya T. ; Behm, Carolyn A. ; Hall, David H. ; Mathesius, Ulrike ; Rug, Melanie ; Nguyen, Ken C.Q. ; Verma, Naresh K. / Shigella flexneri infection in Caenorhabditis elegans : Cytopathological examination and identification of host responses. In: PLoS One. 2014 ; Vol. 9, No. 9.
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