Identification and characterization of FtsH mediating in vivo colonization and stress adaptation in the fish pathogen Edwardsiella piscicida

Edwardsiella piscicida is an important pathogenic enteric bacterium of fish. FtsH is a unique membrane-anchored AAA + protease that regulates protein homeostasis in bacteria. In cooperation with modulators HflK and HflC, FtsH is essential in enteric bacteria and controls the response to environmental stresses. Here, we used in vivo pattern analysis of conditional essentiality (PACE) and identified that ftsH and hflK/C were associated with impaired in vivo colonization in Edw. piscicida and attenuated internalization ability of ZF4 cells. The ftsH mutant displayed increased survival during prolonged treatment of starvation and high osmotic stresses in Edw. piscicida. Further analysis showed that the disruption of ftsH resulted in the overproduction of the established substrate LpxC, which is responsible for the synthesis of LPS (lipopolysaccharide), as well as the substrate YfgM, which is involved in high osmolality tolerance during stationary phase. However, the inconsistency in the abilities of the ftsH and hflK/C mutants to achieve YfgM-based osmotic resistance indicated that there might be multiple, while distinctive, pathways controlled by FtsH and the associated modulator proteins HflK/C. This investigation revealed the unique functions of FtsH and its modulator HflK/C in Edw. piscicida.