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Yersinia pestis and Yersinia pseudotuberculosis infection: a regulatory RNA perspective.

Martínez-Chavarría LC, Vadyvaloo V - Front Microbiol (2015)

Bottom Line: An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes.One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species.Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Patología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, México Mexico.

ABSTRACT
Yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, Y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species. Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors. Here the burgeoning field of small non-coding regulatory RNAs in Yersinia pathogenesis is reviewed from the viewpoint of adaptive colonization, virulence and divergent evolution of these pathogens.

No MeSH data available.


Related in: MedlinePlus

Common (black font) and exclusively expressed (red font) sRNA repertoires are found in Yersinia pestis strains of genetically distinct backgrounds in four separate studies using different growth conditions. Common sRNAs are represented by all their annotated names (these are separated by a slash) from different Yersinia and E. coli studies. Exclusively expressed consecutive sRNAs are not separately named, instead an encompassing dash indicates that they compose the list. Those non-consecutive exclusively expressed sRNAs are named singly and separated by commas from other sRNAs. Each study identifying a sRNA repertoire is represented in the Venn diagram by a different color and denoted according to the first author and year of publication of the study.
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Figure 1: Common (black font) and exclusively expressed (red font) sRNA repertoires are found in Yersinia pestis strains of genetically distinct backgrounds in four separate studies using different growth conditions. Common sRNAs are represented by all their annotated names (these are separated by a slash) from different Yersinia and E. coli studies. Exclusively expressed consecutive sRNAs are not separately named, instead an encompassing dash indicates that they compose the list. Those non-consecutive exclusively expressed sRNAs are named singly and separated by commas from other sRNAs. Each study identifying a sRNA repertoire is represented in the Venn diagram by a different color and denoted according to the first author and year of publication of the study.

Mentions: While there exists some overlap in the sRNA sets discovered in each of these studies, there are a large number of potential sRNAs that are unique to each study as exemplified in a comparison of Y. pestis sRNAs identified in the four studies above (Figure 1, Supplementary Table S2). The variable sRNA expression profiles in the studies are likely a consequence of several experimental factors: (1) specific experimental culture conditions, e.g., medium composition, temperature, phase of growth, in vivo vs. in vitro, (2) species and strains, e.g., Y. pestis vs. Y. pseudotuberculosis or Y. pestis CO92 vs. Y. pestis KIM6+ (3) methodologies used, e.g., deep sequencing vs. cDNA cloning, (4) bioinformatics analysis and pipelines applied to data, e.g., expression cut-off thresholds. However other intrinsic factors could also impact variable expression of sRNAs. Take for instance a scenario in which Y. pestis and Y. pseudotuberculosis encode the same sRNA but that this sRNAs controls different mRNAs targets in the two species, which in turn are additionally differentially regulated by distinct global regulators or growth conditions. In this case, the expression of the sRNA will vary according to the availability of its targets, as in the absence of the mRNA target the sRNA is subject to destabilization and rapid degradation. Indeed, it has been demonstrated that conserved sRNAs between Y. pseudotuberculosis and Y. pestis can differ in stability and/or expression (Koo et al., 2011; Beauregard et al., 2013). Furthermore, many of the sRNAs that are encoded and expressed by both species contain single nucleotide variations, mismatches, insertions or deletions which could alter the RNA secondary structure and result in distinct interactions with target mRNAs between the species. Some other sRNAs are duplicated, like RyhB (Ysr146.1 and Ysr146.2) in Y. pseudotuberculosis, which is regulated by the iron level. It would be interesting to analyze if those duplicated sRNAs have different roles in response to different environmental conditions during the infection and accordingly, if they control the expression of different sets of genes. An added complication can occur during infection if only a fraction of the cell population expresses a particular sRNA. For example, it has been shown that only a small fraction of either Y. pseudotuberculosis or Y. pestis bacterial populations express the sRNAs Ysr35 or Ysp8, at low copy numbers of 0 to 10 transcripts per cell. Such low quantities can be difficult to detect, limiting identification of such sRNAs (Shepherd et al., 2013). Certainly these differences in sRNA expression between the two pathogens are responsible for some of the divergent clinical disease outcomes.


Yersinia pestis and Yersinia pseudotuberculosis infection: a regulatory RNA perspective.

Martínez-Chavarría LC, Vadyvaloo V - Front Microbiol (2015)

Common (black font) and exclusively expressed (red font) sRNA repertoires are found in Yersinia pestis strains of genetically distinct backgrounds in four separate studies using different growth conditions. Common sRNAs are represented by all their annotated names (these are separated by a slash) from different Yersinia and E. coli studies. Exclusively expressed consecutive sRNAs are not separately named, instead an encompassing dash indicates that they compose the list. Those non-consecutive exclusively expressed sRNAs are named singly and separated by commas from other sRNAs. Each study identifying a sRNA repertoire is represented in the Venn diagram by a different color and denoted according to the first author and year of publication of the study.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585118&req=5

Figure 1: Common (black font) and exclusively expressed (red font) sRNA repertoires are found in Yersinia pestis strains of genetically distinct backgrounds in four separate studies using different growth conditions. Common sRNAs are represented by all their annotated names (these are separated by a slash) from different Yersinia and E. coli studies. Exclusively expressed consecutive sRNAs are not separately named, instead an encompassing dash indicates that they compose the list. Those non-consecutive exclusively expressed sRNAs are named singly and separated by commas from other sRNAs. Each study identifying a sRNA repertoire is represented in the Venn diagram by a different color and denoted according to the first author and year of publication of the study.
Mentions: While there exists some overlap in the sRNA sets discovered in each of these studies, there are a large number of potential sRNAs that are unique to each study as exemplified in a comparison of Y. pestis sRNAs identified in the four studies above (Figure 1, Supplementary Table S2). The variable sRNA expression profiles in the studies are likely a consequence of several experimental factors: (1) specific experimental culture conditions, e.g., medium composition, temperature, phase of growth, in vivo vs. in vitro, (2) species and strains, e.g., Y. pestis vs. Y. pseudotuberculosis or Y. pestis CO92 vs. Y. pestis KIM6+ (3) methodologies used, e.g., deep sequencing vs. cDNA cloning, (4) bioinformatics analysis and pipelines applied to data, e.g., expression cut-off thresholds. However other intrinsic factors could also impact variable expression of sRNAs. Take for instance a scenario in which Y. pestis and Y. pseudotuberculosis encode the same sRNA but that this sRNAs controls different mRNAs targets in the two species, which in turn are additionally differentially regulated by distinct global regulators or growth conditions. In this case, the expression of the sRNA will vary according to the availability of its targets, as in the absence of the mRNA target the sRNA is subject to destabilization and rapid degradation. Indeed, it has been demonstrated that conserved sRNAs between Y. pseudotuberculosis and Y. pestis can differ in stability and/or expression (Koo et al., 2011; Beauregard et al., 2013). Furthermore, many of the sRNAs that are encoded and expressed by both species contain single nucleotide variations, mismatches, insertions or deletions which could alter the RNA secondary structure and result in distinct interactions with target mRNAs between the species. Some other sRNAs are duplicated, like RyhB (Ysr146.1 and Ysr146.2) in Y. pseudotuberculosis, which is regulated by the iron level. It would be interesting to analyze if those duplicated sRNAs have different roles in response to different environmental conditions during the infection and accordingly, if they control the expression of different sets of genes. An added complication can occur during infection if only a fraction of the cell population expresses a particular sRNA. For example, it has been shown that only a small fraction of either Y. pseudotuberculosis or Y. pestis bacterial populations express the sRNAs Ysr35 or Ysp8, at low copy numbers of 0 to 10 transcripts per cell. Such low quantities can be difficult to detect, limiting identification of such sRNAs (Shepherd et al., 2013). Certainly these differences in sRNA expression between the two pathogens are responsible for some of the divergent clinical disease outcomes.

Bottom Line: An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes.One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species.Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Patología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, México Mexico.

ABSTRACT
Yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, Y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species. Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors. Here the burgeoning field of small non-coding regulatory RNAs in Yersinia pathogenesis is reviewed from the viewpoint of adaptive colonization, virulence and divergent evolution of these pathogens.

No MeSH data available.


Related in: MedlinePlus