| Summary: | Campylobacter jejuni (C. jejuni) is the leading cause of bacterial gastroenteritis in the developed world. Despite the prevalence of C. jejuni as a human pathogen, relatively little is known about it's precise pathogenesis mechanisms, particularly in comparison to other well-studied enteric pathogens like E. coli and Salmonella spp. Altered expression of phosphate genes in a C.jejuni stringent response mutant, together with known correlations between the stringent response, polyphosphate (poly P), and virulence in other pathogens, led us to investigate the role of poly P in C. jejuni physiology and pathogenesis. All sequenced C. jejuni strains harbour a conserved putative polyphosphate kinase (PPK1) predicted to be principally responsible for poly P synthesis. We generated a targeted ppkl deletion mutant (Δppk1) in C. jejuni strain 81-176 and found that this mutant, as well as the ΔspoT stringent response mutant, exhibited low levels of poly P at all growth stages. In contrast, wild-type C. jejuni poly P levels increased significantly as the bacteria transitioned from log to stationary phase. Phenotypic analyses revealed that the Δppk1 mutant was defective for survival during osmotic shock and low-nutrient stress. However, certain phenotypes associated with ppk1 deletion in other bacteria (i.e., motility, oxidative stress) were unaffected in the C. jejuni mutant, which also displayed a surprising increase in biofilm formation. The C. jejuni Δppk1 mutant was also defective for the virulence-associated phenotype of intra-epithelial cell survival in a tissue culture infection model and exhibited a striking defect in dose-dependent chick colonization. These results indicate that poly P utilization and accumulation contribute significantly to C. jejuni pathogenesis and affect its ability to adapt to specific stresses and stringencies. Furthermore, our study demonstrates that poly P likely plays both similar and unique roles in C. jejuni compared to other bacteria, and that poly P metabolism is linked with stringent response mechanisms in C. jejuni. === Science, Faculty of === Microbiology and Immunology, Department of === Graduate
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