• Shigella dysenteriae
• Whole Cell Lysate
• Staphylococcus aureus
• Periplasm, Cell Envelope & Cell Wall
• Streptococcus pneumoniae
• Whole Cell Lysate
• Yersinia pestis
• Periplasm, Cell Envelope & Cell Wall
• Membrane
• Poster Presentations

The Shigella dysenteriae serotype 1 proteome, profiled in the host intestinal environment, reveals major metabolic modifications and increased expression of invasive proteins

¹, Quanshun Zhang², Prashanth P Parmar¹, Shih-Ting Huang¹, David J Clark¹, Hamid Alami¹, Arthur Donohue-Rolfe², Robert D Fleischmann¹, Scott N Peterson¹ and Saul Tzipori²

¹Pathogen Functional Genomics Resource Center, J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD 20850, USA

²Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, MA 01536, USA

(Article accepted for publication: Proteomics, August 12, 2009)

Abstract

Shigella dysenteriae serotype 1 (SD1) causes the most severe form of epidemic bacillary dysentery. We present the first comprehensive 2D gel-based proteome analysis of this pathogen, profiling proteins from bacteria cultured in vitro with bacterial isolates from the large bowel of infected gnotobiotic piglets (in vivo). Overall, 1061 distinct gene products were identified. Differential display analysis revealed that SD1 cells switched to an anaerobic energy metabolism in vivo. High in vivo abundances of the protein disaggregation chaperones HdeA, HdeB and ClpB and the amino acid decarboxylases GadB and AdiA, which enhance pH homeostasis in the cytoplasm, were indicative of a coordinated bacterial survival response to acid stress. Several type III secretion effectors were increased in abundance in vivo. This included IpaC, IpaD, OspC2 and OspF; the latter three have been implicated in invasion of colonocytes and subversion of the host immune response in S. flexneri. The outer membrane protein OmpA, the heat shock protein HtpG and OspC2 were detected as strong antigens in western blots using a piglet antiserum. These observations reflect protein activity-based adaptive responses of SD1 cells to a hostile host environment and resulted in the identification of an intriguing set of drug and subunit vaccine targets.

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