Cell entry and exit by periodontal pathogen via recycling pathway

In the oral cavity, gingival epithelial cell (GEC) layers function as an innate host defense system to prevent intrusion by periodontal bacteria. Nevertheless, Porphyromonas gingivalis, the most well-known periodontal pathogen, can enter GECs and pass through the epithelial barrier into deeper tissues. An intracellular location is considered advantageous for bacteria to escape from immune surveillance by the host as well as antibiotic pressure, leading to intracellular persistence, multiplication, and dissemination to adjacent tissues. P. gingivalis are invaginated by gingival epithelial cells via the endocytic pathway, and some intracellular bacteria are sorted to lytic compartments, including autolysosomes and late endosomes/lysosomes, while a considerable number of the remaining organisms are sorted to Rab11- and RalA-positive recycling endosomes, followed by bacterial exit from the cells. Exited bacteria can re-enter fresh cells. However, dominant negative forms and RNAi-knockdown of Rab11, RalA, and exocyst complex subunits (Sec5, Sec6, and Exo84) significantly disturb the exit of P. gingivalis. These are the first known results to show that the endocytic recycling pathway mediates bacterial exit from infected cells to neighboring cells and may provide important information regarding the exit mechanisms of various invasive pathogens.