1
The quorum-hindered transcription factor YenR of Yersinia enterocolitica inhibits pheromone production and promotes motility via a small non-coding RNA.
Mol Microbiol. 2011 Apr; 80(2):556-71
All selected articles haveThis article has been added to your saved articles
You can follow/unfollow articles via MyF1000 or via the article or browse pages.
24 May 2011
New Finding
DOI: 10.3410/f.10676956.11561054
In this paper, the authors have discovered a novel regulatory mechanism for 'quorum hindering' in Yersinia enterocolitica, in which the apo-form of the LuxR orthologue YenR drives the expression of a small untranslated RNA termed YenS. This functions to inhibit the translation and accumulation of the...Continue reading
In this paper, the authors have discovered a novel regulatory mechanism for 'quorum hindering' in Yersinia enterocolitica, in which the apo-form of the LuxR orthologue YenR drives the expression of a small untranslated RNA termed YenS. This functions to inhibit the translation and accumulation of the yenI mRNA transcript and, hence, N-acylhomoserine lactone (AHL) synthesis and quorum sensing (QS).
QS is a common regulatory mechanism that enables a bacterium to coordinate gene expression as a function of cell population density through the production of one or more QS signal molecules. It plays a pivotal role in the lifestyle of both beneficial and pathogenic bacteria by facilitating mutually beneficial behavior. Many Gram-negative bacteria employ a LuxR/LuxI/AHL-type QS system in which the AHL synthesized via a LuxI orthologue binds to and activates a LuxR orthologous regulator protein. Most AHLs are autoinducers since the luxI promoter is usually a target for the LuxR/AHL complex. Depending on the LuxR orthologue, AHLs may activate either by facilitating protein folding or by dimerization. However, not all LuxR homologues are activators; some act as repressors only active in the absence of their cognate AHLs, while others may function as both activators and repressors depending on the population density and prevailing AHL concentrations.
In the present paper, the authors describe an elegant mechanism for quorum 'hindering' in the Gram-negative bacterium Y. enterocolitica, which produces the AHLs N-(3-oxohexanoyl)homoserine lactone (3-oxo-C6-HSL) and N-hexanoylhomoserine lactone (C6-HSL) via the yenI gene located adjacent to, but divergent from, yenR. Although the yenR/yenI system regulates swimming and swarming motility in Y. enterocolitica {1}, the direct targets for YenR have not been identified. Consequently, chromatin immunoprecipitation experiments in a yenI mutant expressing yenR (which is locked in the low-density state) are undertaken and an intergenic region upstream of the yenR translation start site is identified among a number of putative YenR targets. This locus contains two sites (yen boxes), both of which bind apo-YenR non-cooperatively with high affinity and both are found to be required for the full activation of an upstream gene termed yenS, coding for a small untranslated regulatory RNA. YenR activates yenS but only in the apo-form, while YenS inhibites AHL production by binding to the yenI mRNA, so blocking its translation. At low cell population densities yenS expression is elevated, but decreases as the population density increased.
Two different mechanisms through which a YenR/YenS/YenI-type regulatory cycle may exhibit hysteresis (i.e. the tendency of a system to remain stable in one of two states despite sub-threshold changes in the local environmental conditions) are proposed by the authors of this interesting paper. The first involves the YenS-mediated inhibition of AHL accumulation that ensures the continuing availability of apo-YenR protein, while the second, more speculative mechanism involves the hybridization of the yenR and yenI mRNA transcripts (the yenR and yenI genes are convergent and overlap) such that at low cell densities apo-YenR increases YenS levels, so reducing yenI mRNA transcript levels. This would result in an excess of yenR mRNA and an accumulation of apo-YenR. At high cell densities, the accumulation of YenR-AHL complexes would lead to a reduction in yenS expression, an increase in yenI transcription and so raise AHL levels.
Phenotypically, the contribution of YenS to the QS-dependent control of swarming motility is demonstrated by the loss of hypermotility in a yenI mutant following the mutation of yenS (or yenR) or provision of exogenous 3-oxo-C6-HSL, data that also imply a direct positive role for YenS. In other Y. enterocolitica yenI mutant strains, complementation with a multi-copy plasmid carrying yenI restores motility, whereas the provision of exogenous AHLs has no effect {1}, an unexpected finding that might also be explained via yenS/yenI mRNA interactions.
Regulatory cycles coupling the action of a small RNA to the modulation of a QS system may prove to be more widespread than currently appreciated, since YenS is conserved in other Yersinia species. Furthermore, in Pantoea stewartii, a small regulatory RNA (esaS) unrelated to YenS is located upstream of esaR, stimulated by apo-EsaR and inhibited by the cognate AHL {2}. NB – I am listed as an author on ref {1}.
QS is a common regulatory mechanism that enables a bacterium to coordinate gene expression as a function of cell population density through the production of one or more QS signal molecules. It plays a pivotal role in the lifestyle of both beneficial and pathogenic bacteria by facilitating mutually beneficial behavior. Many Gram-negative bacteria employ a LuxR/LuxI/AHL-type QS system in which the AHL synthesized via a LuxI orthologue binds to and activates a LuxR orthologous regulator protein. Most AHLs are autoinducers since the luxI promoter is usually a target for the LuxR/AHL complex. Depending on the LuxR orthologue, AHLs may activate either by facilitating protein folding or by dimerization. However, not all LuxR homologues are activators; some act as repressors only active in the absence of their cognate AHLs, while others may function as both activators and repressors depending on the population density and prevailing AHL concentrations.
In the present paper, the authors describe an elegant mechanism for quorum 'hindering' in the Gram-negative bacterium Y. enterocolitica, which produces the AHLs N-(3-oxohexanoyl)homoserine lactone (3-oxo-C6-HSL) and N-hexanoylhomoserine lactone (C6-HSL) via the yenI gene located adjacent to, but divergent from, yenR. Although the yenR/yenI system regulates swimming and swarming motility in Y. enterocolitica {1}, the direct targets for YenR have not been identified. Consequently, chromatin immunoprecipitation experiments in a yenI mutant expressing yenR (which is locked in the low-density state) are undertaken and an intergenic region upstream of the yenR translation start site is identified among a number of putative YenR targets. This locus contains two sites (yen boxes), both of which bind apo-YenR non-cooperatively with high affinity and both are found to be required for the full activation of an upstream gene termed yenS, coding for a small untranslated regulatory RNA. YenR activates yenS but only in the apo-form, while YenS inhibites AHL production by binding to the yenI mRNA, so blocking its translation. At low cell population densities yenS expression is elevated, but decreases as the population density increased.
Two different mechanisms through which a YenR/YenS/YenI-type regulatory cycle may exhibit hysteresis (i.e. the tendency of a system to remain stable in one of two states despite sub-threshold changes in the local environmental conditions) are proposed by the authors of this interesting paper. The first involves the YenS-mediated inhibition of AHL accumulation that ensures the continuing availability of apo-YenR protein, while the second, more speculative mechanism involves the hybridization of the yenR and yenI mRNA transcripts (the yenR and yenI genes are convergent and overlap) such that at low cell densities apo-YenR increases YenS levels, so reducing yenI mRNA transcript levels. This would result in an excess of yenR mRNA and an accumulation of apo-YenR. At high cell densities, the accumulation of YenR-AHL complexes would lead to a reduction in yenS expression, an increase in yenI transcription and so raise AHL levels.
Phenotypically, the contribution of YenS to the QS-dependent control of swarming motility is demonstrated by the loss of hypermotility in a yenI mutant following the mutation of yenS (or yenR) or provision of exogenous 3-oxo-C6-HSL, data that also imply a direct positive role for YenS. In other Y. enterocolitica yenI mutant strains, complementation with a multi-copy plasmid carrying yenI restores motility, whereas the provision of exogenous AHLs has no effect {1}, an unexpected finding that might also be explained via yenS/yenI mRNA interactions.
Regulatory cycles coupling the action of a small RNA to the modulation of a QS system may prove to be more widespread than currently appreciated, since YenS is conserved in other Yersinia species. Furthermore, in Pantoea stewartii, a small regulatory RNA (esaS) unrelated to YenS is located upstream of esaR, stimulated by apo-EsaR and inhibited by the cognate AHL {2}. NB – I am listed as an author on ref {1}.
References
1.
Quorum sensing in Yersinia enterocolitica controls swimming and swarming motility.
J Bacteriol 2006 Feb; 4(188):1451-61
PMID: 16452428
2.
Structure/function analysis of the Pantoea stewartii quorum-sensing regulator EsaR as an activator of transcription.
J Bacteriol 2009 Dec; 24(191):7402-9
PMID: 19820098
Disclosures
None declared
Add Comment
Williams P: F1000Prime Recommendation of [Tsai CS and Winans SC, Mol Microbiol 2011, 80(2):556-71]. In F1000Prime, 24 May 2011; DOI: 10.3410/f.10676956.11561054. F1000Prime.com/10676956#eval11561054
F1000Prime Recommendations, Dissents and Comments for [Tsai CS and Winans SC, Mol Microbiol 2011, 80(2):556-71]. In F1000Prime, 23 May 2013; F1000Prime.com/10676956
Only registered/signed-in users can make comments.
Sign in or Subscribe to create your user account and join the discussion.
Sign in or Subscribe to create your user account and join the discussion.
No comments yet.
The YenR and YenI proteins of Yersinia enterocolitica resemble the quorum sensing proteins LuxR and LuxI of Vibrio fischeri. Apo-YenR activated a gene, designated yenS, that lies adjacent to and divergent from yenR. YenR-dependent expression of yenS was inhibited by endogenous or exogenous 3-oxohexanoylhomoserine lactone (OHHL) a pheromone made by YenI. Purified apo-YenR bound non-cooperatively to two 20-nucleotide sites that lie upstream of yenS. Binding occurred in the absence of (OHHL), and YenR was largely released from the DNA by this pheromone. yenS encoded two non-translated RNAs 169 and 105 nucleotides long that share the same 5' end but have different 3' ends. One or both RNAs inhibited the translation and accumulation of the yenI mRNA by binding to a region that overlaps the YenI start codon. A mutation in yenI strongly stimulated swarming motility on the surface of semi-solid agar, while exogenous OHHL completely suppressed this phenotype. Hypermotility in yenI mutants was also suppressed by mutations in yenR or yenS, suggesting that YenS plays a direct, stimulatory role in swarming motility.
© 2011 Blackwell Publishing Ltd.
DOI: 10.1111/j.1365-2958.2011.07595.x
PMID: 21362062
