Regulatory Elements Implicated in the Environmental Control of Invasin Expression in Enteropathogenic Yersinia

Abstract

During infections of the intestinal tract Yersinia pseudotuberculosis penetrates the epithelial cell layer through M-cells into the Peyer's patches. This early step in the infection process is primarily mediated by the outer membrane protein invasin. Expression of the invasin gene is activated by the MarR-type regulatory protein RovA in response to environmental conditions, including temperature and growth phase. In order to gain insight into the nature of the underlying control systems, mutagenesis and gene bank screens were used to identify regula components modulating the levels of invasin and RovA. We found that the inv and rovA genes were both subjected to silencing by the nucleoid-associated protein H-NS. Under inducing conditions, RovA appears to disrupt the silencer complex, through displacement of H-NS from an extended AT-rich region located upstream of the inv and rovA promoters. Furthermore, a LysR-type regulatory protein, RovM with homology to HexA/PecT of phytopathogenic Erwinia species was shown to interact specifically with the rovA regulatory region and represses rovA transcription in addition to H-NS. Disruption of the rovM gene significantly enhanced internalization of Y. pseudotuberculosis into host cells and higher numbers of the mutant bacteria were detectable in gut-associated lymphatic tissues and organs in infected mice. In addition, the histone-like protein YmoA, which has a global effect on the bacterial physiology, was found to activate rovA expression through RovM. Together, our studies showed, that H-NS, RovM and YmoA are key regulators implicated in the environmental control of virulence factors, which are important for the initiation of a Yersinia infection.

Anti-silencing: overcoming H-NS-mediated repression of transcription in Gram-negative enteric bacteria

“…(Nasser & Reverchon, 2002), Proteus mirabilis (Coker et al, 2000), Shigella flexneri Prosseda et al, 2004), Vibrio cholerae (Ghosh et al, 2006;Nye et al, 2000) and Yersinia spp. (Cathelyn et al, 2007;Ellison & Miller, 2006b;Heroven et al, 2007).…”

“…Here, the invasin gene inv is repressed by a silencing complex consisting of H-NS and an extended region of A+T-rich DNA at the inv promoter. When the bacterium is grown under invinducing conditions, RovA displaces H-NS from the silencing element, leading to transcription of the inv gene (Heroven et al, 2007).…”

“…Much like the VirB regulon in Shigella flexneri, antisilencing of the RovA regulon is also integrated into the H-NS regulon. In Y. pseudotuberculosis, the repression of rovA by H-NS is reinforced by a co-repressor, RovM, a protein related to LysR-like transcription factors, bringing an opportunity for fine-tuning the operation of the antisilencing mechanism (Heroven et al, 2007).…”

Thermosensing to Adjust Bacterial Virulence in a Fluctuating Environment

“…Transcriptional activator of virulence genes; binds to DNA as homodimer at 20-25°C, defolds partially at higher temperatures and looses its DNA binding capacity; multisensor: salicylate prevents DNA-binding of RovA [137,139,142] Listeria monocytogenes MogR:GmaR MogR binds to flagella genes and represses transcription at 37°C; anti-repressor GmaR binds MogR at 30°C; in complex no repression; GmaR misfolds at 37°C and MogR:GmaR complex disassembles [150,152,153,155] Agrobacterium tumefaciens VirA Two-component system VirAG activates transcription of vir genes only below 32°C; sensor kinase VirA changes conformation at high temperatures and is inactive [4] Pseudomonas syringae CorS Two-component system CorSR activates transcripttion of phytotoxin biogenesis genes at 18°C; at 28°C: rearrangements of the transmembrane domains of the sensor kinase CorS prevent autophosphorylation and/or phosphotransfer to response regulator [177,178] Streptococci M-like proteins Class C proteins bind to plasma proteins low temperatures as coiled coils; homodimers disrupt at 37°C; C-repeats seem to be thermosensitive Cedervall 1995Cedervall 1997 …”

An iron-regulated LysR-type element mediates antimicrobial peptide resistance and virulence in Yersinia pseudotuberculosis

“…Concomitantly, we studied two transcription controls: (i) the iron transporter-encoding gene yfeA, which is induced by iron restriction (Bearden et al, 1998), and (ii) the invasin-encoding gene inv, which is ironindependent (Heroven et al, 2007). As shown in Fig.…”