The Yersinia enterocolitica type three secretion chaperone SycO is integrated into the Yop regulatory network and binds to the Yop secretion protein YscM1

Abstract

Background: Pathogenic yersiniae (Y. pestis, Y. pseudotuberculosis, Y. enterocolitica) share a virulence plasmid encoding a type three secretion system (T3SS). This T3SS comprises more than 40 constituents. Among these are the transport substrates called Yops (Yersinia outer proteins), the specific Yop chaperones (Sycs), and the Ysc (Yop secretion) proteins which form the transport machinery. The effectors YopO and YopP are encoded on an operon together with SycO, the chaperone of YopO. The characterization of SycO is the focus of this study.

Control of gene expression by type III secretory activity

“…The corresponding decrease in the intracellular levels of these proteins then relieves the block on yop translation. In reality, however, the regulatory system is much more complicated with the potential for extensive cross-talk between type III secretion chaperones and secretion substrates (YscY, the chaperone for YscX which is essential for secretory activity, also interacts with LcrH; SycH, the chaperone for YscM1/M2 also interacts with YopH; SycO, the chaperone for YopO, also interacts with YscM1; and SycE, the chaperone for YopE also interacts with YscM1/M2) [40][41][42].…”

Interrelationship between type three secretion system and metabolism in pathogenic bacteria

“…In other words, how can inhibition of PEPC activity by YscM1/LcrQ explain growth restriction given that the YscM1/LcrQ level in Yersinia is low under these conditions? Perhaps this has to do with the complex protein/protein interaction network in which these regulators are intertwined with at least seven possible interaction partners besides PEPC (Cambronne et al, 2000 ; Swietnicki et al, 2004 ; Dittmann et al, 2007 ; Wilharm et al, 2007 ; Li et al, 2014a , b ). Moreover, there is also evidence that PEPC is not the only junction between the YscM proteins and metabolism in Yersinia .…”

Cross-talk between Type Three Secretion System and Metabolism in Yersinia

“…This "load-andshoot cycle" model states that functioning of the T3SS in vivo requires a reprogramming of metabolic pathways and that it is the bifunctionality of YscM/LcrQ that allows coordination of Yop expression and metabolism. YscM/LcrQ interact with a multitude of T3SS proteins, mostly T3SS chaperones, which prompted us to speculate that YscM/LcrQ proteins function as a molecular interface that senses if T3SS chaperones are loaded with Yops and transduces this information into repression or derepression of Yop synthesis in concert with YopD, LcrH, and SycH (14,31). In parallel, this integrated information is also ideally suited to coordinate the metabolism via modulation of PEPC activity and possibly other metabolic enzymes.…”

“…Perspectives-The YscM/LcrQ proteins interact with several components of the T3SS and represent major nodal points of the T3SS regulatory network (14,31). A complete T3SS interactome is therefore required to elucidate the significance of the PEPC/YscM interactions.…”

“…The primers used were 5Ј-CTAACAACCCTGCGGCGTCAAGGGCGAA-GGGGATATGGGTCAGGGGTCATTCACTGACACCCTC-ATCAGTG-3Ј and 5Ј-ACGGGCGCCTGGCCCGTTTTGTC-TTTTATTCACGATAATTCTACTGGCAACGTCAAGTC-AGCGTAATGCTC-3Ј. Construction of yscM1 and yscM2 deletion strains was previously described (31). After cleavage of pWS with NdeI and SalI, appropriate inserts with PCR-introduced NdeI and SalI sites, respectively, were ligated.…”