Different invasion phenotypes of Campylobacter isolates in Caco-2 cell monolayers

Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire SP4 0JG 1 Corresponding author: Miss P. Harvey (e-mail: philippa.harvey@camr.org.uk). Received May 21, 1998 Revision received August 7, 1998. Accepted August 7, 1998 The pathogenesis of campylobacter enteritis is not well understood, but invasion into and translocation across intestinal epithelial cells may be involved in the disease process, as demonstrated for a number of other enteric pathogens. However, the mechanisms involved in these processes are not clearly defined for campylobacters. In this study, isolates were compared quantitatively in established assays with the enterocyte-like cell line, Caco-2, to determine the extent to which intracellular invasion contributes to translocation across epithelial cell monolayers, and whether isolates vary in this respect. Ten fresh Campylobacter isolates were compared and shown to differ in invasiveness by a factor of 10-fold by following their recovery from gentamicin-treated Caco-2 cells grown on non-permeable tissue-culture wells. Four of these isolates with contrasting invasive ability were also shown to vary in their ability to translocate across Caco-2 cells grown on semi-permeable Transwell inserts by a factor >10. However, translocation did not quantitatively correlate with the intracellular invasiveness of these isolates. Isolate no. 9752 was poorly invasive but had modest translocation ability, isolate no. 10392 was very invasive but did not translocate significantly and remained within the monolayer, isolate no. 9519 both translocated and invaded well, whereas, isolate no. 235 translocated very efficiently but was poorly invasive. Isolate no. 9519 also uniquely caused a transitory flattening of the Caco-2 cells and a possible drop in trans-epithelial electrical resistance (TEER) of the Transwell monolayers, whereas isolate no. 235 did not show these effects. Together these data demonstrate that there are significantly different ‘invasion’ phenotypes among Campylobacter strains involving different degrees of intracellular invasion, and either different rates of transcellular trafficking or, alternatively, paracellular trafficking.