Polyphosphate and associated enzymes as global regulators of stress response and virulence in Campylobacter jejuni

Abstract

Campylobacter jejuni (C. jejuni), a Gram-negative microaerophilic bacterium, is a predominant cause of bacterial foodborne gastroenteritis in humans worldwide. Despite its importance as a major foodborne pathogen, our understanding of the molecular mechanisms underlying C. jejuni stress survival and pathogenesis is limited. Inorganic polyphosphate (poly P) has been shown to play significant roles in bacterial resistance to stress and virulence in many pathogenic bacteria. C. jejuni contains the complete repertoire of enzymes required for poly P metabolism. Recent work in our laboratory and others have demonstrated that poly P controls a plethora of C. jejuni properties that impact its ability to survive in the environment as well as to colonize/infect mammalian hosts. This review article summarizes the current literature on the role of poly P in C. jejuni stress survival and virulence and discusses on how poly P-related enzymes can be exploited for therapeutic/prevention purposes. Additionally, the review article identifies potential areas for future investigation that would enhance our understanding of the role of poly P in C. jejuni and other bacteria, which ultimately would facilitate design of effective therapeutic/preventive strategies to reduce not only the burden of C. jejuni-caused foodborne infections but also of other bacterial infections in humans.

Keywords: Campylobacter jejuni; Colonization/infection; Inorganic polyphosphate; Stress tolerance; Virulence.

Figure 1

Model of poly P metabolism in Campylobacter jejuni. Phosphate esters are hydrolyzed to inorganic phosphate (Pi) by alkaline phosphatase (PhoAcj) in the periplasm. Phosphate uptake proteins and alkaline phosphatase are directly regulated by the PhosS/PhosR two-component system. Pi is transported across the inner membrane via the high affinity phosphate transport system PstSCAB. ATP generated from Pi is utilized for poly P synthesis by PPK1. PPK2 utilizes poly P to generate GTP, while PPX hydrolyzes poly P back to Pi. PPX also affects conversion of (p)ppGpp to ppGpp. SpoT is a bifunctional enzyme involved in both ppGpp synthesis as well as ppGpp hydrolysis. SpoT is also linked to poly P metabolism and a spoT mutant has reduced ability to accumulate poly P.