Campylobacter jejuni CsrA Regulates Metabolic and Virulence Associated Proteins and Is Necessary for Mouse Colonization

Abstract

Campylobacter jejuni infection is a leading bacterial cause of gastroenteritis and a common antecedent leading to Gullian-Barré syndrome. Our previous data suggested that the RNA-binding protein CsrA plays an important role in regulating several important phenotypes including motility, biofilm formation, and oxidative stress resistance. In this study, we compared the proteomes of wild type, csrA mutant, and complemented csrA mutant C. jejuni strains in an effort to elucidate the mechanisms by which CsrA affects virulence phenotypes. The putative CsrA regulon was more pronounced at stationary phase (111 regulated proteins) than at mid-log phase (25 regulated proteins). Proteins displaying altered expression in the csrA mutant included diverse metabolic functions, with roles in amino acid metabolism, TCA cycle, acetate metabolism, and various other cell processes, as well as pathogenesis-associated characteristics such as motility, chemotaxis, oxidative stress resistance, and fibronectin binding. The csrA mutant strain also showed altered autoagglutination kinetics when compared to the wild type. CsrA specifically bound the 5’ end of flaA mRNA, and we demonstrated that CsrA is a growth-phase dependent repressor of FlaA expression. Finally, the csrA mutant exhibited reduced ability to colonize in a mouse model when in competition with the wild type, further underscoring the role of CsrA in C. jejuni colonization and pathogenesis.

Catabolite repression in Campylobacter jejuni correlates with intracellular succinate levels

“…GOGAT activity was similar for all strains tested, except for the csrA mutant strain. The csrA gene codes for a post‐transcriptional regulator and has previously been implicated in metabolic regulation (Fields et al ., ). The GOGAT activity was more than twice as high in the csrA mutant strain, compared to the wt and the other strains (Fig.…”

“…Since both the gltB and the ggt 5′UTR mRNA do not form a required stem loop for CsrA binding (data not shown) (Radomska et al ., ), these effects are likely to be indirect. A previous CsrA proteomics study found higher GGT protein levels, but not GOGAT (Fields et al ., ). It is unclear why our results are different, but this could be due to the use of other culture media and growth conditions.…”

“…A C. jejuni csrA mutant strain however, showed elevated GOGAT activity and slightly increased GGT activity in the exponential growth phase compared to the wt. CsrA is a post-transcriptional regulator that is involved in regulation of central metabolic pathways, motility, biofilm, cell invasion and flagella synthesis (Fields et al, 2016;Radomska et al, 2016). Since both the gltB and the ggt 5 0 UTR mRNA do not form a required stem loop for CsrA binding (data not shown) (Radomska et al, 2016), these effects are likely to be indirect.…”

Adhesion of Campylobacter jejuni Is Increased in Association with Foodborne Bacteria

“…It is known that C. jejuni can adhere to different inert surfaces (e.g., stainless steel, glass fibre, beads and coverslips, nitrocellulose membranes, various plastics) [2,3,5,6] and living surfaces (e.g., animal and human intestinal cell lines) [5][6][7][8][9][10]. Cell adhesion to these surfaces is followed by biofilm formation, as an advanced protection mechanism against environmental stresses, antimicrobial agents, and shaking at 75 rpm.…”

Global Regulation by CsrA and Its RNA Antagonists

“…In the wake of early evidence that CsrA (RsmA) influences the expression of other regulators (18,104), transcriptomics and other studies have uncovered vast potential for bacterial Csr systems to interact with other regulators and global regulatory systems (e.g. 12,13,20,[24][25][26][27][28][29][30][31][32][33][34][35]. Most of these interactions have not been further investigated, but in a few cases the integration of transcriptional and Csr posttranscriptional regulatory circuitry have been studied.…”