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Coregulation of host-adapted metabolism and virulence by pathogenic yersiniae.

Heroven AK, Dersch P - Front Cell Infect Microbiol (2014)

Bottom Line: In order to manage rapidly changing environmental conditions and interbacterial competition, Yersinia senses the nutritional composition during the course of an infection by special molecular devices, integrates this information and adapts its metabolism accordingly.Recent studies revealed that global regulatory factors such as the cAMP receptor protein (Crp) and the carbon storage regulator (Csr) system are part of a large network of transcriptional and posttranscriptional control strategies adjusting metabolic changes and virulence in response to temperature, ion and nutrient availability.Gained knowledge about the specific metabolic requirements and the correlation between metabolic and virulence gene expression that enable efficient host colonization led to the identification of new potential antimicrobial targets.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Institut für Mikrobiology, Technische Universität Braunschweig Braunschweig, Germany.

ABSTRACT
Deciphering the principles how pathogenic bacteria adapt their metabolism to a specific host microenvironment is critical for understanding bacterial pathogenesis. The enteric pathogenic Yersinia species Yersinia pseudotuberculosis and Yersinia enterocolitica and the causative agent of plague, Yersinia pestis, are able to survive in a large variety of environmental reservoirs (e.g., soil, plants, insects) as well as warm-blooded animals (e.g., rodents, pigs, humans) with a particular preference for lymphatic tissues. In order to manage rapidly changing environmental conditions and interbacterial competition, Yersinia senses the nutritional composition during the course of an infection by special molecular devices, integrates this information and adapts its metabolism accordingly. In addition, nutrient availability has an impact on expression of virulence genes in response to C-sources, demonstrating a tight link between the pathogenicity of yersiniae and utilization of nutrients. Recent studies revealed that global regulatory factors such as the cAMP receptor protein (Crp) and the carbon storage regulator (Csr) system are part of a large network of transcriptional and posttranscriptional control strategies adjusting metabolic changes and virulence in response to temperature, ion and nutrient availability. Gained knowledge about the specific metabolic requirements and the correlation between metabolic and virulence gene expression that enable efficient host colonization led to the identification of new potential antimicrobial targets.

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Schematic overview of regulatory factors that are known to coordinate expression of metabolic functions but also virulence-associated traits in pathogenic Yersinia species. It should be noted that not all regulatory networks have been experimentally verified in all pathogenic yersiniae.
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Figure 3: Schematic overview of regulatory factors that are known to coordinate expression of metabolic functions but also virulence-associated traits in pathogenic Yersinia species. It should be noted that not all regulatory networks have been experimentally verified in all pathogenic yersiniae.

Mentions: Global regulators that govern complex networks and cascades of control elements in a concerted manner achieve coordination of metabolic pathways with pathogenicity mechanisms. One important global transcriptional factor known to control metabolism and pathogenicity in all three human pathogenic Yersinia species is Crp. Crp binds the signal metabolite cAMP produced by the adenylate cyclase in the absence of glucose or other efficiently utilizable sugars (Hanamura and Aiba, 1991; Ishizuka et al., 1994). Crp also represses expression of the adenylate cyclase gene cyaA (Qu et al., 2013). The cAMP-Crp complex controls at least 6% of the genes in Y. pestis and Y. pseudotuberculosis, including genes required for growth on different C-sources, survival under carbon, nitrogen, and phosphate limitation as well as virulence (Gosset et al., 2004; Heroven et al., 2012b; Zhan et al., 2008, 2009). In Y. pestis, expression of crp is crucial for the development of bubonic and pneumonic plague. Most likely this is based on the function of Crp as regulator of the T3SS/Yop machinery and the plasminogen activator protease Pla (Kim et al., 2007; Liu et al., 2009; Zhan et al., 2008, 2009; Lathem et al., 2014). In Y. enterocolitica, a crp mutant strain was shown to be strongly attenuated in an oral infection model, and Crp-mediated influence on the expression of the flagellar, Ysc/Yop, and the Ysa T3SS is anticipated to contribute to loss of virulence (Petersen and Young, 2002). Similarly, Crp is required for colonization and/or persistence of Y. pseudotuberculosis in the MLNs and organs later during infection (Heroven et al., 2012b). In our recent study using comparative metabolomics, transcriptomics and a phenotypic microarray analysis, we could demonstrate that Crp of Y. pseudotuberculosis promotes oxidative catabolism of many different C-sources, whereas it represses fermentative patterns. Furthermore, it links carbon metabolism to the regulation of virulence factors via the control of the virulence-associated small RNAs CsrC and CsrB of the Csr system (Heroven et al., 2012b) (Figure 3).


Coregulation of host-adapted metabolism and virulence by pathogenic yersiniae.

Heroven AK, Dersch P - Front Cell Infect Microbiol (2014)

Schematic overview of regulatory factors that are known to coordinate expression of metabolic functions but also virulence-associated traits in pathogenic Yersinia species. It should be noted that not all regulatory networks have been experimentally verified in all pathogenic yersiniae.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202721&req=5

Figure 3: Schematic overview of regulatory factors that are known to coordinate expression of metabolic functions but also virulence-associated traits in pathogenic Yersinia species. It should be noted that not all regulatory networks have been experimentally verified in all pathogenic yersiniae.
Mentions: Global regulators that govern complex networks and cascades of control elements in a concerted manner achieve coordination of metabolic pathways with pathogenicity mechanisms. One important global transcriptional factor known to control metabolism and pathogenicity in all three human pathogenic Yersinia species is Crp. Crp binds the signal metabolite cAMP produced by the adenylate cyclase in the absence of glucose or other efficiently utilizable sugars (Hanamura and Aiba, 1991; Ishizuka et al., 1994). Crp also represses expression of the adenylate cyclase gene cyaA (Qu et al., 2013). The cAMP-Crp complex controls at least 6% of the genes in Y. pestis and Y. pseudotuberculosis, including genes required for growth on different C-sources, survival under carbon, nitrogen, and phosphate limitation as well as virulence (Gosset et al., 2004; Heroven et al., 2012b; Zhan et al., 2008, 2009). In Y. pestis, expression of crp is crucial for the development of bubonic and pneumonic plague. Most likely this is based on the function of Crp as regulator of the T3SS/Yop machinery and the plasminogen activator protease Pla (Kim et al., 2007; Liu et al., 2009; Zhan et al., 2008, 2009; Lathem et al., 2014). In Y. enterocolitica, a crp mutant strain was shown to be strongly attenuated in an oral infection model, and Crp-mediated influence on the expression of the flagellar, Ysc/Yop, and the Ysa T3SS is anticipated to contribute to loss of virulence (Petersen and Young, 2002). Similarly, Crp is required for colonization and/or persistence of Y. pseudotuberculosis in the MLNs and organs later during infection (Heroven et al., 2012b). In our recent study using comparative metabolomics, transcriptomics and a phenotypic microarray analysis, we could demonstrate that Crp of Y. pseudotuberculosis promotes oxidative catabolism of many different C-sources, whereas it represses fermentative patterns. Furthermore, it links carbon metabolism to the regulation of virulence factors via the control of the virulence-associated small RNAs CsrC and CsrB of the Csr system (Heroven et al., 2012b) (Figure 3).

Bottom Line: In order to manage rapidly changing environmental conditions and interbacterial competition, Yersinia senses the nutritional composition during the course of an infection by special molecular devices, integrates this information and adapts its metabolism accordingly.Recent studies revealed that global regulatory factors such as the cAMP receptor protein (Crp) and the carbon storage regulator (Csr) system are part of a large network of transcriptional and posttranscriptional control strategies adjusting metabolic changes and virulence in response to temperature, ion and nutrient availability.Gained knowledge about the specific metabolic requirements and the correlation between metabolic and virulence gene expression that enable efficient host colonization led to the identification of new potential antimicrobial targets.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Institut für Mikrobiology, Technische Universität Braunschweig Braunschweig, Germany.

ABSTRACT
Deciphering the principles how pathogenic bacteria adapt their metabolism to a specific host microenvironment is critical for understanding bacterial pathogenesis. The enteric pathogenic Yersinia species Yersinia pseudotuberculosis and Yersinia enterocolitica and the causative agent of plague, Yersinia pestis, are able to survive in a large variety of environmental reservoirs (e.g., soil, plants, insects) as well as warm-blooded animals (e.g., rodents, pigs, humans) with a particular preference for lymphatic tissues. In order to manage rapidly changing environmental conditions and interbacterial competition, Yersinia senses the nutritional composition during the course of an infection by special molecular devices, integrates this information and adapts its metabolism accordingly. In addition, nutrient availability has an impact on expression of virulence genes in response to C-sources, demonstrating a tight link between the pathogenicity of yersiniae and utilization of nutrients. Recent studies revealed that global regulatory factors such as the cAMP receptor protein (Crp) and the carbon storage regulator (Csr) system are part of a large network of transcriptional and posttranscriptional control strategies adjusting metabolic changes and virulence in response to temperature, ion and nutrient availability. Gained knowledge about the specific metabolic requirements and the correlation between metabolic and virulence gene expression that enable efficient host colonization led to the identification of new potential antimicrobial targets.

Show MeSH
Related in: MedlinePlus