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Regulatory principles governing Salmonella and Yersinia virulence.

Erhardt M, Dersch P - Front Microbiol (2015)

Bottom Line: In order to manage sudden environmental changes, attacks by the host immune systems and microbial competition, the pathogens employ a plethora of transcriptional and post-transcriptional control elements, including transcription factors, sensory and regulatory RNAs, RNAses, and proteases, to fine-tune and control complex gene regulatory networks.However, the interplay, arrangement, and composition of the control elements vary between these closely related enteric pathogens, which generate phenotypic differences leading to distinct pathogenic properties.We highlight evolutionary changes of the gene regulatory circuits that result in different properties of the regulatory elements and how this influences the overall outcome of the infection process.

View Article: PubMed Central - PubMed

Affiliation: Young Investigator Group Infection Biology of Salmonella, Helmholtz Centre for Infection Research Braunschweig, Germany.

ABSTRACT
Enteric pathogens such as Salmonella and Yersinia evolved numerous strategies to survive and proliferate in different environmental reservoirs and mammalian hosts. Deciphering common and pathogen-specific principles for how these bacteria adjust and coordinate spatiotemporal expression of virulence determinants, stress adaptation, and metabolic functions is fundamental to understand microbial pathogenesis. In order to manage sudden environmental changes, attacks by the host immune systems and microbial competition, the pathogens employ a plethora of transcriptional and post-transcriptional control elements, including transcription factors, sensory and regulatory RNAs, RNAses, and proteases, to fine-tune and control complex gene regulatory networks. Many of the contributing global regulators and the molecular mechanisms of regulation are frequently conserved between Yersinia and Salmonella. However, the interplay, arrangement, and composition of the control elements vary between these closely related enteric pathogens, which generate phenotypic differences leading to distinct pathogenic properties. In this overview we present common and different regulatory networks used by Salmonella and Yersinia to coordinate the expression of crucial motility, cell adhesion and invasion determinants, immune defense strategies, and metabolic adaptation processes. We highlight evolutionary changes of the gene regulatory circuits that result in different properties of the regulatory elements and how this influences the overall outcome of the infection process.

No MeSH data available.


Related in: MedlinePlus

Regulatory networks controlling Yersinia virulence factors. Regulatory networks controlling expression of motility, adhesion and injectisome virulence traits in Yersinia. Direct or indirect regulatory effects of various factors are indicated.
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Figure 3: Regulatory networks controlling Yersinia virulence factors. Regulatory networks controlling expression of motility, adhesion and injectisome virulence traits in Yersinia. Direct or indirect regulatory effects of various factors are indicated.

Mentions: External stimuli, which are relevant for metabolic adaptation and virulence are frequently sensed by bacterial two component systems (TCSs) and converted into an adaptive cellular response. Among the most virulence-relevant TCS are the pleiotropic PhoP/PhoQ, EnvZ/OmpR, and BarA/SirA(UvrY) systems (Groisman, 2001; Groisman and Mouslim, 2006) (Figures 2 and 3). They are composed of the membrane-bound sensor kinases PhoQ, EnvZ, and BarA that sense the environmental signals and phosphorylate the cytoplasmic response regulator PhoP, OmpR, and UvrY(SirA). The TCS PhoP/PhoQ responds to low magnesium, low pH environments, and host-secreted cationic antimicrobial peptides (Groisman, 2001). The global regulator PhoP controls a very complex network of genes, whereby the individual Yersinia and Salmonella PhoP regulons have considerable differences: (i) in the molecular architecture of the regulatory sequences and promoters, and (ii) in amino acid alterations in the conserved PhoP regulator itself. This enables both PhoP response regulators to retain the ability to transcribe the core members of the regulon in both pathogens and also allows inclusion of newly acquired genes into the ancestral regulatory circuit (Perez and Groisman, 2009). In Salmonella, the PhoP/PhoQ system is essential for virulence and survival within macrophages (Miller et al., 1989). The response regulator PhoP represses hilA and the prg (PhoP-repressed genes) genes (Pegues et al., 1995; Bajaj et al., 1996), whereas transcription of PhoP-activated genes (pag) required for survival within macrophages is activated (Miller et al., 1989; Belden and Miller, 1994). PhoP also controls expression of Salmonella pathogenicity island-2 (Spi-2) by binding to the ssrB promoter region and the 5′-UTR of the spiR transcript (Belden and Miller, 1994). In contrast, in yersiniae the PhoP/PhoQ system has been found to promote proliferation of human pathogenic yersiniae within professional phagocytes in vitro, but its role during pathogenesis is less defined (Grabenstein et al., 2004, 2006; Flamez et al., 2007). Recent studies indicate that strain-specific differences that remodel expression of PhoP-dependent control functions appear to influence the overall outcome of the virulence phenotype (Grabenstein et al., 2004; Bozue et al., 2011; Nuss et al., 2014; Pisano et al., 2014). The PhoP/PhoQ system of Yersinia was shown to control modification of lipid A linked to antimicrobial peptide resistance and promotes survival and proliferation in macrophages and neutrophils (Grabenstein et al., 2004; Reines et al., 2012). Another important virulence control system, which is under PhoP/PhoQ control, is the carbon storage regulator (Csr) system coordinating the expression of important Yersinia adhesion factors (e.g., invasin), motility and multiple virulence-relevant metabolic pathways (see also Conclusion and Outlook; Heroven et al., 2008; Bücker et al., 2014; Nuss et al., 2014).


Regulatory principles governing Salmonella and Yersinia virulence.

Erhardt M, Dersch P - Front Microbiol (2015)

Regulatory networks controlling Yersinia virulence factors. Regulatory networks controlling expression of motility, adhesion and injectisome virulence traits in Yersinia. Direct or indirect regulatory effects of various factors are indicated.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563271&req=5

Figure 3: Regulatory networks controlling Yersinia virulence factors. Regulatory networks controlling expression of motility, adhesion and injectisome virulence traits in Yersinia. Direct or indirect regulatory effects of various factors are indicated.
Mentions: External stimuli, which are relevant for metabolic adaptation and virulence are frequently sensed by bacterial two component systems (TCSs) and converted into an adaptive cellular response. Among the most virulence-relevant TCS are the pleiotropic PhoP/PhoQ, EnvZ/OmpR, and BarA/SirA(UvrY) systems (Groisman, 2001; Groisman and Mouslim, 2006) (Figures 2 and 3). They are composed of the membrane-bound sensor kinases PhoQ, EnvZ, and BarA that sense the environmental signals and phosphorylate the cytoplasmic response regulator PhoP, OmpR, and UvrY(SirA). The TCS PhoP/PhoQ responds to low magnesium, low pH environments, and host-secreted cationic antimicrobial peptides (Groisman, 2001). The global regulator PhoP controls a very complex network of genes, whereby the individual Yersinia and Salmonella PhoP regulons have considerable differences: (i) in the molecular architecture of the regulatory sequences and promoters, and (ii) in amino acid alterations in the conserved PhoP regulator itself. This enables both PhoP response regulators to retain the ability to transcribe the core members of the regulon in both pathogens and also allows inclusion of newly acquired genes into the ancestral regulatory circuit (Perez and Groisman, 2009). In Salmonella, the PhoP/PhoQ system is essential for virulence and survival within macrophages (Miller et al., 1989). The response regulator PhoP represses hilA and the prg (PhoP-repressed genes) genes (Pegues et al., 1995; Bajaj et al., 1996), whereas transcription of PhoP-activated genes (pag) required for survival within macrophages is activated (Miller et al., 1989; Belden and Miller, 1994). PhoP also controls expression of Salmonella pathogenicity island-2 (Spi-2) by binding to the ssrB promoter region and the 5′-UTR of the spiR transcript (Belden and Miller, 1994). In contrast, in yersiniae the PhoP/PhoQ system has been found to promote proliferation of human pathogenic yersiniae within professional phagocytes in vitro, but its role during pathogenesis is less defined (Grabenstein et al., 2004, 2006; Flamez et al., 2007). Recent studies indicate that strain-specific differences that remodel expression of PhoP-dependent control functions appear to influence the overall outcome of the virulence phenotype (Grabenstein et al., 2004; Bozue et al., 2011; Nuss et al., 2014; Pisano et al., 2014). The PhoP/PhoQ system of Yersinia was shown to control modification of lipid A linked to antimicrobial peptide resistance and promotes survival and proliferation in macrophages and neutrophils (Grabenstein et al., 2004; Reines et al., 2012). Another important virulence control system, which is under PhoP/PhoQ control, is the carbon storage regulator (Csr) system coordinating the expression of important Yersinia adhesion factors (e.g., invasin), motility and multiple virulence-relevant metabolic pathways (see also Conclusion and Outlook; Heroven et al., 2008; Bücker et al., 2014; Nuss et al., 2014).

Bottom Line: In order to manage sudden environmental changes, attacks by the host immune systems and microbial competition, the pathogens employ a plethora of transcriptional and post-transcriptional control elements, including transcription factors, sensory and regulatory RNAs, RNAses, and proteases, to fine-tune and control complex gene regulatory networks.However, the interplay, arrangement, and composition of the control elements vary between these closely related enteric pathogens, which generate phenotypic differences leading to distinct pathogenic properties.We highlight evolutionary changes of the gene regulatory circuits that result in different properties of the regulatory elements and how this influences the overall outcome of the infection process.

View Article: PubMed Central - PubMed

Affiliation: Young Investigator Group Infection Biology of Salmonella, Helmholtz Centre for Infection Research Braunschweig, Germany.

ABSTRACT
Enteric pathogens such as Salmonella and Yersinia evolved numerous strategies to survive and proliferate in different environmental reservoirs and mammalian hosts. Deciphering common and pathogen-specific principles for how these bacteria adjust and coordinate spatiotemporal expression of virulence determinants, stress adaptation, and metabolic functions is fundamental to understand microbial pathogenesis. In order to manage sudden environmental changes, attacks by the host immune systems and microbial competition, the pathogens employ a plethora of transcriptional and post-transcriptional control elements, including transcription factors, sensory and regulatory RNAs, RNAses, and proteases, to fine-tune and control complex gene regulatory networks. Many of the contributing global regulators and the molecular mechanisms of regulation are frequently conserved between Yersinia and Salmonella. However, the interplay, arrangement, and composition of the control elements vary between these closely related enteric pathogens, which generate phenotypic differences leading to distinct pathogenic properties. In this overview we present common and different regulatory networks used by Salmonella and Yersinia to coordinate the expression of crucial motility, cell adhesion and invasion determinants, immune defense strategies, and metabolic adaptation processes. We highlight evolutionary changes of the gene regulatory circuits that result in different properties of the regulatory elements and how this influences the overall outcome of the infection process.

No MeSH data available.


Related in: MedlinePlus