| Summary: | Campylobacter jejuni is the leading cause of foodborne bacterial gastroenteritis in the developed world. Although
illness is usually self-limiting, immunocompromised individuals are at risk for infections recalcitrant to
antibiotic treatment. Prior infection with C. jejuni also correlates with serious sequelae such as Guillain-Barré
syndrome. The success of C. jejuni as a zoonotic pathogen indicates it can adapt to varied conditions
encountered during pathogenesis, despite apparent fastidiousness in the lab. Understanding how C. jejuni
survives in common reservoirs may allow development of strategies to limit survival in infection reservoirs or
during pathogenesis, and greatly reduce the impact of C. jejuni-mediated disease. A two-component regulatory
system, (CprRS; Campylobacter planktonic growth regulation) was previously identified in a screen for genes
that may be required for adaptation to the host. Subsequent characterization of CprRS has contributed to
understanding of two themes related to C. jejuni survival: environmental gene regulation and biofilm
formation. The CprR response regulator was essential for viability, and while the CprS sensor kinase was
dispensable, a ΔcprS mutant showed significant phenotypic differences from WT. Initial characterization of
ΔcprS using phenotypic and proteomic means provided evidence that CprRS affects phenomena related to
biofilm formation. Further characterization of CprRS was undertaken through transcriptomics of ΔcprS,
molecular analysis of CprR, and promoter analysis. The CprRS regulon suggests that the system may control
aspects of the cell envelope, including expression of the HtrA periplasmic protease. Finally, subsequent
analysis of the biofilm-enhanced ΔcprS mutant, together with epistatic analyses and analysis of WT C. jejuni
under stress conditions, has provided insight into C. jejuni biofilm initiation, maturation, and physiology. A
specific role for flagella in biofilm initiation was demonstrated, and lysis and extracellular DNA release during
biofilm maturation was also observed. Furthermore, evidence that the C. jejuni biofilm lifestyle confers stress
tolerance that is not present in planktonic counterparts was obtained. Characterization of CprRS has thus
contributed to knowledge of both physiological and regulatory themes that provide C. jejuni, a pathogen
which diverges from paradigms set out in model bacteria, with its surprising resilience during zoonosis, and
has also identified novel targets for infection control.
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