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Polyphosphate kinase 1 (PPK1) is a pathogenesis determinant in Campylobacter jejuni Candon, Heather L.

Abstract

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.

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