Authors:Rogier Louwen, P. van Baarlen, A. H. M. van Vliet, A. van Belkum, J. P. Hays and H. P. Endtz
Bacteria belonging to the species Campylobacter are the most common cause of bacterial diarrhoea in humans. The clinical phenotype associated with Campylobacter infections ranges from asymptomatic conditions to severe colitis and bacteremia. In susceptible patients, Campylobacter infections are associated with significant morbidity and mortality, with both host factors and bacterial factors being involved in the pathogenesis of bacteremia. In the host, age, gender and immune-compromising conditions may predispose for Campylobacter infections, whilst the most important bacterial determinants mentioned in the literature are cytotoxin production and flagellar motility. The role of sialylated lipo-oligosaccharide (LOS) and serum resistance in bacteremia is inconclusive at this time, and the clinical significance of Campylobacter bacteremia is not yet fully understood. More emphasis on the detection of Campylobacter species from blood cultures in susceptible patients at risk for Campylobacter infections will increase our understanding of the pathogenesis and the relevance of Campylobacter bacteremia.
Authors:M. T. Le, I. Porcelli, C. M. Weight, D. J. H. Gaskin, S. R. Carding and A. H. M. van Vliet
The bacterial pathogen Campylobacter jejuni is the leading cause of foodborne gastroenteritis in the developed world, with the organism being transmitted by ingestion of contaminated and undercooked poultry. Exposure to acid is an inevitable stressor for C. jejuni during gastric passage, yet the effect of low pH on C. jejuni virulence is still poorly understood. Here, we investigate the effect of acid-shock on C. jejuni viability, gene expression and host-cell invasion. C. jejuni strain NCTC 11168 survived acid exposure at pH 3.5 and above for up to 30 min without a drop in viability, and this exposure induced the expression of flagellar genes transcribed from σ54-dependent promoters. Furthermore, acid-shock resulted in increased C. jejuni invasion of m-ICcl2 mouse small intestine crypt cells grown on transwells, but not when the cells were grown on flat-bottomed wells. This suggests that C. jejuni might be invading intestinal epithelial cells at the basolateral side, possibly after paracellular passage. We hypothesize that acid-shock prior to intestinal entry may serve as a signal that primes C. jejuni to express its virulence gene repertoire including flagellar motility genes, but this requires further study in the context of an appropriate colonization or disease model.
Authors:C. Belzer, B. A. M. van Schendel, T. Hoogenboezem, J. G. Kusters, P. W. M. Hermans, A. H. M. van Vliet and E. J. Kuipers
Chronic intestinal and hepatic colonization with the microaerophilic murine pathogen Helicobacter hepaticus can lead to a range of inflammatory diseases of the lower digestive tract. Colonization is associated with an active cellular immune response and production of oxygen radicals. During colonization, H. hepaticus needs to cope with and respond to oxidative stress, and here we report on the role of the H. hepaticus PerR-regulator (HH0942) in the expression of the peroxidase-encoding katA (HH0043) and ahpC (HH1564) genes. Transcription of katA and ahpC was induced by hydrogen peroxide, and by iron restriction of growth media. This iron- and hydrogen peroxide-responsive regulation of katA and ahpC was mediated at the transcriptional level, from promoters directly upstream of the genes. Inactivation of the perR gene resulted in constitutive, iron-independent high-level expression of the katA and ahpC transcripts and corresponding proteins. Finally, inactivation of the katA gene resulted in increased sensitivity of H. hepaticus to hydrogen peroxide and reduced aerotolerance. In H. hepaticus, iron metabolism and oxidative stress defense are intimately connected via the PerR regulatory protein. This regulatory pattern resembles that observed in the enteric pathogen Campylobacter jejuni, but contrasts with the pattern observed in the closely related human gastric pathogen Helicobacter pylori.