Phosphate transporter PstSCAB of Campylobacter jejuni is a critical determinant of lactate-dependent growth and colonization in chickens

Campylobacter jejuni causes acute gastroenteritis world-wide and is transmitted primarily through poultry, in which it is often a commensal member of the intestinal microbiota. Previous RNASeq experiments showed that transcripts from an operon encoding a high affinity phosphate transporter (PstSCAB) of C. jejuni were among the most abundant when grown in chickens. Elevated levels of the pstSCAB mRNA were also identified in an RNASeq experiment from human infection studies. In this study, we explore the role of PstSCAB in the biology and colonization potential of C. jejuni. Our experimental results demonstrate that cells lacking PstSCAB survive poorly in stationary phase, nutrient-limiting media, and under osmotic conditions reflective of those in the chicken. Polyphosphate levels in the mutant cells were elevated at stationary phase, consistent with alterations in expression of polyphosphate metabolism genes. C. jejuni were highly attenuated in colonization of newly hatched chicks, recovered at levels several orders of magnitude below wild type. Mutant and wild type grew similarly in complex media but the pstS::kan mutant exhibited a significant growth defect in minimal media supplemented with L-lactate, postulated as a carbon source in vivo. Poor growth in lactate correlated with diminished expression of acetogenesis pathway genes previously demonstrated as important for colonizing chickens. The phosphate transport system is thus essential for diverse aspects of C. jejuni physiology and in vivo fitness and survival. Importance:Campylobacter jejuni causes millions of human gastrointestinal infections annually, with poultry a major source of infection. Due to the emergence of multi-drug resistance in C. jejuni, there is need to identify alternative ways to control this pathogen. Genes encoding the high-affinity phosphate transporter PstSCAB are highly expressed by C. jejuni in chickens and humans. In this study, we address the role of PstSCAB on chicken colonization and other C. jejuni phenotypes. PstSCAB is required for colonization in chicken, metabolism and survival under different stress responses and during growth on lactate, a potential growth substrate in chickens. Our study highlights that PstSCAB may be an effective target to develop mechanisms to control the bacterial burden in both chicken and human.