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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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Metabolic pathways and virulence factors of Y. pestis induced in the flea and the mammalian host. Metabolic functions and pathogenicity traits upregulated in vivo are illustrated which are considered to be important for colonization of the flea gut (in blue) and the lung or bubo of the mammalian host (in red). The red box marks genes shown to be required for full virulence of Y. pestis in the bubo of infected rats (Pradel et al., 2014).
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Figure 2: Metabolic pathways and virulence factors of Y. pestis induced in the flea and the mammalian host. Metabolic functions and pathogenicity traits upregulated in vivo are illustrated which are considered to be important for colonization of the flea gut (in blue) and the lung or bubo of the mammalian host (in red). The red box marks genes shown to be required for full virulence of Y. pestis in the bubo of infected rats (Pradel et al., 2014).

Mentions: The in vivo transcriptome of Y. pestis in the proventriculus of infected fleas revealed numerous metabolic genes involved in the adaptation to the flea gut (Vadyvaloo et al., 2010). Flea meals appear to consist primarily of proteins and lipids with low amounts of carbohydrates. Thus, it is not surprising that mainly amino acids, in particular the L-glutamate group (e.g., glutamine, histidine, arginine, proline) are catabolized by Y. pestis in the flea vector (Figure 2). Degradation of these amino acids results in an increased flux of the amino acid carbon through the TCA cycle, the enzymatic genes for which are highly induced in the flea (Vadyvaloo et al., 2010). In contrast, catabolism of hexoses seems not to be important. The glucose PTS is only slightly increased and most other sugar uptake systems are repressed. An exception is the PTS uptake and utilization system for chitobiose, a C-source that is present in the flea's proventriculus spines (Figure 2). During growth in the digestive system of the flea synthesis of most important virulence factors, e.g., the T3SS/Yop apparatus, the iron sequestration systems Ybt, and Yfe, the virulence regulator RovA, and PsaA fimbriae are repressed. However, other crucial pathogenicity genes (e.g., pla, yadBC) and insecticidal-like toxin genes are upregulated (Figure 2). Expression of these genes is critical for dissemination from the extravascular tissue at the fleabite site and seems to preadapt Y. pestis to resist mammalian innate immunity by acquisition of a phagocytosis-resistant phenotype. This may enhance plague pathogenesis in the very early stages while the full set of thermal controlled virulence factors is still not produced (Vadyvaloo et al., 2010). Also genes of the Y. pestis hms operon which are required for the formation of the poly-N-acetylglucosamine (PNAG) surface carbohydrate, a major component of biofilms, were found to be induced at moderate temperature and within fleas. Thus, hms-dependent biofilms were assumed to support colonization of the proventriculus and facilitate transmission of plague bacteria (Hinnebusch et al., 1996; Vadyvaloo et al., 2010). However, a recent report showed that in two other fully virulent Y. pestis strains PNAG synthesis is maximal at 37°C, indicating that this factor may also have a role during mammalian infection (Yoong et al., 2012).


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

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

Metabolic pathways and virulence factors of Y. pestis induced in the flea and the mammalian host. Metabolic functions and pathogenicity traits upregulated in vivo are illustrated which are considered to be important for colonization of the flea gut (in blue) and the lung or bubo of the mammalian host (in red). The red box marks genes shown to be required for full virulence of Y. pestis in the bubo of infected rats (Pradel et al., 2014).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Metabolic pathways and virulence factors of Y. pestis induced in the flea and the mammalian host. Metabolic functions and pathogenicity traits upregulated in vivo are illustrated which are considered to be important for colonization of the flea gut (in blue) and the lung or bubo of the mammalian host (in red). The red box marks genes shown to be required for full virulence of Y. pestis in the bubo of infected rats (Pradel et al., 2014).
Mentions: The in vivo transcriptome of Y. pestis in the proventriculus of infected fleas revealed numerous metabolic genes involved in the adaptation to the flea gut (Vadyvaloo et al., 2010). Flea meals appear to consist primarily of proteins and lipids with low amounts of carbohydrates. Thus, it is not surprising that mainly amino acids, in particular the L-glutamate group (e.g., glutamine, histidine, arginine, proline) are catabolized by Y. pestis in the flea vector (Figure 2). Degradation of these amino acids results in an increased flux of the amino acid carbon through the TCA cycle, the enzymatic genes for which are highly induced in the flea (Vadyvaloo et al., 2010). In contrast, catabolism of hexoses seems not to be important. The glucose PTS is only slightly increased and most other sugar uptake systems are repressed. An exception is the PTS uptake and utilization system for chitobiose, a C-source that is present in the flea's proventriculus spines (Figure 2). During growth in the digestive system of the flea synthesis of most important virulence factors, e.g., the T3SS/Yop apparatus, the iron sequestration systems Ybt, and Yfe, the virulence regulator RovA, and PsaA fimbriae are repressed. However, other crucial pathogenicity genes (e.g., pla, yadBC) and insecticidal-like toxin genes are upregulated (Figure 2). Expression of these genes is critical for dissemination from the extravascular tissue at the fleabite site and seems to preadapt Y. pestis to resist mammalian innate immunity by acquisition of a phagocytosis-resistant phenotype. This may enhance plague pathogenesis in the very early stages while the full set of thermal controlled virulence factors is still not produced (Vadyvaloo et al., 2010). Also genes of the Y. pestis hms operon which are required for the formation of the poly-N-acetylglucosamine (PNAG) surface carbohydrate, a major component of biofilms, were found to be induced at moderate temperature and within fleas. Thus, hms-dependent biofilms were assumed to support colonization of the proventriculus and facilitate transmission of plague bacteria (Hinnebusch et al., 1996; Vadyvaloo et al., 2010). However, a recent report showed that in two other fully virulent Y. pestis strains PNAG synthesis is maximal at 37°C, indicating that this factor may also have a role during mammalian infection (Yoong et al., 2012).

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