YscM1 and YscM2, two Yersinia enterocolitica proteins causing downregulation of yop transcription

Abstract

SummarySynthesis of the Yop proteins by yersiniae is downregulated when secretion is prevented by closure or destruction of the contact (type III) secretion channel. In Yersinia pseudotuberculosis, a mutation in the lcrQ gene, encoding a secreted protein, reduces this feedback inhibition mechanism. Surprisingly, mutation in the yscM gene, the lcrQ homologue in Y. enterocolitica, does not lead to the same deregulated phenotype. In this paper, we addressed the question of this discrepancy. We found a new gene on the Y. enterocolitica pYV plasmid that encodes a protein with 57% identity to YscM (now called YscM1). Overexpression of this gene, called yscM2, like overexpression of lcrQ and yscM1, blocked Yop secretion. A double yscM1, yscM2 mutant had the same phenotype as that of the lcrQ mutant. The discrepancy can thus be explained by the existence of two functionally equivalent copies of yscM in Y. enterocolitica. Overexpression of yscM1 drastically reduced the expression of a yopH-cat reporter gene when tested in a pYV þ background. However, no effect could be observed in the absence of a pYV plasmid, indicating that YscM1 does not act directly as a transcriptional repressor or as an anti-VirF factor. We have also ruled out that YscM acts by obstructing the secretion channel.

Yersinia enterocolitica Type III Secretion: yscM1 and yscM2 Regulate yop Gene Expression by a Posttranscriptional Mechanism That Targets the 5′ Untranslated Region of yop mRNA

“…These mechanisms manipulate the host's innate immune response, thereby preventing bacterial phagocytosis and killing (17). Y. enterocolitica transports 14 proteins via the type III pathway: LcrV, YopB, YopD, YopE, YopH, YopM, YopN, YopO, YopP, YopQ, YopR, YopT, YscM1, and YscM2 (1,19,25,26,32,35,40,41,44,49,52). The genes encoding secretion substrates and type III machinery components are located on a 70-kb virulence plasmid (13).…”

“…Overexpression of lcrQ abolishes yop expression even under condi-tions that induce type III secretion (43,48). Unlike Y. pseudotuberculosis and Y. pestis, each of which harbors a single lcrQ gene, the Y. enterocolitica virulence plasmid encodes two lcrQ homologs, yscM1 and yscM2 (52). Knockout mutations in yscM1 and yscM2, but not single deletions, cause mutant Yersinia strains to overexpress yop genes (52).…”

“…Unlike Y. pseudotuberculosis and Y. pestis, each of which harbors a single lcrQ gene, the Y. enterocolitica virulence plasmid encodes two lcrQ homologs, yscM1 and yscM2 (52). Knockout mutations in yscM1 and yscM2, but not single deletions, cause mutant Yersinia strains to overexpress yop genes (52). Overexpression of each gene alone (yscM1 or yscM2) is sufficient to repress the synthesis of Yops (7,52).…”

“…Knockout mutations in yscM1 and yscM2, but not single deletions, cause mutant Yersinia strains to overexpress yop genes (52). Overexpression of each gene alone (yscM1 or yscM2) is sufficient to repress the synthesis of Yops (7,52). Thus, yscM1 and yscM2 must display overlapping and at least partially redundant functions (52).…”

Transcriptional Regulation inYersinia: An UpdateYersinia: An Update

“…In Y. pseudotuberculosis, another subunit, LcrQ, is co-injected into the target cell along with the Yop effectors (Cambronne et al, 2000). In Y. enterocolitica, two LrcQ counterparts, called YscM1 and YscM2, have been identified (Stainier et al, 1997). LcrQ is a negative regulator of the LCR stimulon.…”