Molecular characterization of the InvE regulator in the secretion of type III secretion translocases in Salmonella enterica serovar Typhimurium

Abstract

The type III secretion systems (T3SSs) are exploited by many Gram-negative pathogenic bacteria to deliver a set of effector proteins into the host cytosol during cell entry. The T3SS of Salmonella enterica serovar Typhimurium is composed of more than 20 proteins that constitute the membrane-associated base, the needle and the tip complex at the distal end of the T3SS needle. Membrane docking and piercing between the T3SS and host cells is followed by the secretion of effector proteins. Therefore, a secretion hierarchy among the substrates of the T3SS is required. The secretion of the pore-forming translocase proteins SipB, SipC and SipD is controlled by the T3SS regulator protein, InvE. During an attempt to identify the regions of InvE that are involved in T3SS regulation, it was observed that the secretion of SipB, SipC and SipD was inhibited when the C-terminal 52 amino acids were removed from InvE. In addition, InvE derivatives lacking the Nterminal 30 and 100 residues were unable to secrete translocases into the culture medium. Interestingly, in the absence of the N-terminal 180 residues of InvE, SipD is unstable, resulting in the hypersecretion of SipB. We also found that both the type III secretion signals of SipB and SptP were functionally interchangeable with the first 30 amino acids of InvE, which could allow the secretion of a reporter protein. These results indicate that InvE may have two functional domains responsible for regulating the secretion of translocases: an N-terminal secretion signal and a Cterminal regulatory domain.

Regulation of Type III Secretion of Translocon and Effector Proteins by the EsaB/EsaL/EsaM Complex in Edwardsiella tarda

“…also contains such a complex (YopN/SycN/YscB/TyeA) that prevents unnecessary secretion of effectors prior to its contact with host cells (20). While YopN and TyeA are present as two individual proteins adjacent to each other in Yersinia spp., the homologues of YopN and TyeA in other bacteria appear to fuse with each other and form a single protein, including C. pneumoniae CopN (21), Shigella flexneri MxiC (22), Salmonella InvE (23), and SepL in enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) (24)(25)(26).…”

SalmoNet, an integrated network of ten Salmonella enterica strains reveals common and distinct pathways to host adaptation

“…Recent evidence points to the modulation of metabolism (both of the Salmonella and the host) as yet another mechanism employed by Salmonella to acquire nutrients, evade host defense and survive under harsh intracellular conditions. 51 – 59 …”

Dynamics of sequestration-based gene regulatory cascades

“…A third regulator SipC sequesters SicA, which prevents SicA from interacting with InvF until SipC is exported (18). A fourth regulator InvE interacts with SipC and controls its secretion (48,49). In all four systems shown in Figure 7, indirect anti-activator negative feedback loops are present (ExsD, UsfX, HrpV or SipC).…”