The PagN protein mediates invasion via interaction with proteoglycan.

Heparan sulphate proteoglycans are major components of the mammalian cell membrane. Here we show that PagN of Salmonella enterica serovar Typhimurium utilizes heparinated proteoglycan to successfully invade mammalian cells. Mutants defective in the production of the outer membrane protein PagN displayed similar levels of invasiveness of glycosylation-deficient pgsA-745 cells in comparison with wild-type Salmonella. Furthermore, pgsA-745 cells were invaded c. 400-fold less efficiently than CHO-K1 cells by Escherichia coli expressing PagN. PagN is likely to interact with heparinated proteoglycan as heparin could inhibit PagN-mediated invasion in a dose-dependent manner. Finally, we show, by deletion analysis, that all four extracellular loops of PagN are crucial for invasion of mammalian cells.