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The Campylobacter jejuni stringent response controls specific stress survival and virulence‐associated phenotypes
Author(s) -
Gaynor Erin C.,
Wells Derek H.,
MacKichan Joanna K.,
Falkow Stanley
Publication year - 2005
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2005.04525.x
Subject(s) - biology , virulence , campylobacter jejuni , microbiology and biotechnology , phenotype , gene , microarray , campylobacter , mutant , pathogen , genetics , gene expression , bacteria
Summary Campylobacter jejuni is a highly prevalent food‐borne pathogen that causes diarrhoeal disease in humans. A natural zoonotic, it must overcome significant stresses both in vivo and during transmission despite the absence of several traditional stress response genes. Although relatively little is understood about its mechanisms of pathogenesis, its ability to interact with and invade human intestinal epithelial cells closely correlates with virulence. A C. jejuni microarray‐based screen revealed that several known virulence genes and several uncharacterized genes, including spoT , were rapidly upregulated during infection of human epithelial cells. spoT and its homologue relA have been shown in other bacteria to regulate the stringent response, an important stress response that to date had not been demonstrated for C. jejuni or any other epsilon‐proteobacteria. We have found that C. jejuni mounts a stringent response that is regulated by spoT . Detailed analyses of a C. jejuni Δ spoT mutant revealed that the stringent response is required for several specific stress, transmission and antibiotic resistance‐related phenotypes. These include stationary phase survival, growth and survival under low CO 2 /high O 2 conditions, and rifampicin resistance. A secondary suppressor strain that specifically rescues the low CO 2 growth defect of the Δ spoT mutant was also isolated. The stringent response additionally proved to be required for the virulence‐related phenotypes of adherence, invasion, and intracellular survival in two human epithelial cell culture models of infection; spoT is the first C. jejuni gene shown to participate in longer term survival in epithelial cells. Microarray analyses comparing wild‐type to the Δ spoT mutant also revealed a strong correlation between gene expression profiles and phenotype differences observed. Together, these data demonstrate a critical role for the C. jejuni stringent response in multiple aspects of C. jejuni biology and pathogenesis and, further, may lend novel insight into unexplored features of the stringent response in other prokaryotic organisms.