Interaction Between Type ?- And Type ?-secretion System In Pseudomonas Aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen that can cause acute and chronic infections in multiple parts of the host due to its strong environmental adaptability.Moreover,the drug resistance produced by it is difficult to control with antibiotics,and in recent years has become one of the main pathogens causing nosocomial infections.A large number of studies have shown that the key to pathogenesis is the precise delivery of virulence factors by bacteria to host cells,and the secretory system of bacteria plays a key role.Bacterial cells often use a variety of secretory systems to gain a competitive advantage and survive in different environment.The pathogenicity of Pseudomonas aeruginosa was closely related to its multiple secretory systems in previous studies.Type VI secretion system(T6SS)is widely distributed protein translocation pathway that is known to directly target bacterial and eukaryotic cells or as weapons for interbacterial competition.Type II secretion system(T2SS)can transport a set of proteins out of the cell.Pseudomonas aeruginosa encodes three distinct T6 SS clusters(H1-T6 SS,H2-T6 SS and H3-T6SS)and three T2 SS pathways(Hxc-T2 SS,Txc-T2 SS and Xcp-T2SS).Yet how the interaction between T2 SS and T6 SS is not been reported.Here,we report that the T6 SS cytoplasmic tube Hcp1 interacts with Hxc-T2 SS component HxcX,which allows for functional interaction each other.Our data revealed that HxcX is required for H1-T6 SS secretion,assembly and H1-T6SS-mediated antibacterial activity.We also demonstrated that the conserved phosphate homeostasis regulator,PhoB,regulates the expression of H1-T6 SS directly and influences H1-T6 SS assembly under phosphate limited conditions.In addition,the secretion of Hxc-T2SS-dependent substrate LapA was affected by H1-T6 SS and regulated by PhoB/PhoR and RetS-Gac-Rsm systems.These findings demonstrate that T2 SS and T6 SS may act as a complementary mechanism when eitherpathway becomes limiting.Our results on the T2 SS and T6 SS cross-talk exemplify how Pseudomonas aeruginosa exploit these systems to adapt bacterial behavior to complex environments.This is the first report unraveling the interplay between type VI-and type IIsecretion system,which will expand our knowledge of secretion systems biology and provide important insights for understanding how bacterial adapt to the complex environments.