UPTAKE PATHWAYS OF CLINICAL ISOLATES OF PROTEUS-MIRABILIS INTO HUMAN EPITHELIAL-CELL LINES

Proteus mirabilis isolates obtained from urine and faeces showed high invasion levels into several human epithelial cell lines in gentamicin assays. invasion efficiencies of isolate 102 from a monkey with diarr hoea equalled or even exceeded those of Salmonella typhi strain Ty2 (6 .3 to 13.8% of the inoculum). Vegetative, non-swarming P. mirabilis in vaded epithelial cells efficiently and were found in endosomes and fre e in the cytoplasm. Although inhibition of eukaryotic protein synthesi s by cycloheximide did not reduce bacterial uptake, inhibition with ba cteriostatic antibiotics of bacterial protein-, RNA-, or DNA-synthesis reduced invasion drastically. Involvement of eukaryotic structures an d processes in internalization was determined by using various inhibit ors in the invasion assay. Uptake of P. mirabilis isolated from urine into gut (INT407, HCT-8) cells and bladder (T24) cells was dramaticall y inhibited only by microfilament depolymerization. Internalization of faecal isolate 102 into gut or bladder epithelial cells was inhibited by depolymerization of microfilaments or microtubules. Engulfment of isolate 102 into T24 bladder cells was also reduced by inhibition of r eceptor-mediated endocytosis. Interference with endosome acidification decreased the number of intracellular bacteria of isolate 102 in all three cell lines. These results suggest that P. mirabilis isolates fro m different sources are internalized by epithelial cells by different eukaryotic processes, and that these processes can vary between cell l ines.