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Trigger Enzymes: Coordination of Metabolism and Virulence Gene Expression

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  • Authors: Fabian M. Commichau1, Jörg Stülke2
  • Editor: Tyrrell Conway3
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of General Microbiology, Georg-August-University Göttingen, Grisebachstr. 8, 37077 Göttingen, Germany; 2: Department of General Microbiology, Georg-August-University Göttingen, Grisebachstr. 8, 37077 Göttingen, Germany; 3: University of Oklahoma, Normal, OK
  • Source: microbiolspec July 2015 vol. 3 no. 4 doi:10.1128/microbiolspec.MBP-0010-2014
  • Received 03 August 2014 Accepted 08 August 2014 Published 30 July 2015
  • Jörg Stülke, jstuelk@gwdg.de
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  • Abstract:

    Virulence gene expression serves two main functions, growth in/on the host, and the acquisition of nutrients. Therefore, it is obvious that nutrient availability is important to control expression of virulence genes. In any cell, enzymes are the components that are best informed about the availability of their respective substrates and products. It is thus not surprising that bacteria have evolved a variety of strategies to employ this information in the control of gene expression. Enzymes that have a second (so-called moonlighting) function in the regulation of gene expression are collectively referred to as trigger enzymes. Trigger enzymes may have a second activity as a direct regulatory protein that can bind specific DNA or RNA targets under particular conditions or they may affect the activity of transcription factors by covalent modification or direct protein-protein interaction. In this chapter, we provide an overview on these mechanisms and discuss the relevance of trigger enzymes for virulence gene expression in bacterial pathogens.

  • Citation: Commichau F, Stülke J. 2015. Trigger Enzymes: Coordination of Metabolism and Virulence Gene Expression. Microbiol Spectrum 3(4):MBP-0010-2014. doi:10.1128/microbiolspec.MBP-0010-2014.

Key Concept Ranking

Two-Component Signal Transduction Systems
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/content/journal/microbiolspec/10.1128/microbiolspec.MBP-0010-2014
2015-07-30
2017-11-22

Abstract:

Virulence gene expression serves two main functions, growth in/on the host, and the acquisition of nutrients. Therefore, it is obvious that nutrient availability is important to control expression of virulence genes. In any cell, enzymes are the components that are best informed about the availability of their respective substrates and products. It is thus not surprising that bacteria have evolved a variety of strategies to employ this information in the control of gene expression. Enzymes that have a second (so-called moonlighting) function in the regulation of gene expression are collectively referred to as trigger enzymes. Trigger enzymes may have a second activity as a direct regulatory protein that can bind specific DNA or RNA targets under particular conditions or they may affect the activity of transcription factors by covalent modification or direct protein-protein interaction. In this chapter, we provide an overview on these mechanisms and discuss the relevance of trigger enzymes for virulence gene expression in bacterial pathogens.

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Figures

Image of FIGURE 1
FIGURE 1

In the presence of exogenous proline, the trifunctional PutA enzyme catalyzes the two-step conversion of proline to glutamate, which may serve as a carbon and nitrogen source. This catabolically active, reduced form of PutA (PutA) localizes to the membrane. The divergon, encoding the proline transporter PutP and the PutA trigger enzyme, respectively, is expressed in the presence of proline. In the absence of proline, the oxidized PutA protein (PutA) binds to the intergenic region of the and genes to repress their transcription. P5C, Δ1-pyrroline-5-carboxylate. doi:10.1128/microbiolspec.MBP-0010-2014.f1

Source: microbiolspec July 2015 vol. 3 no. 4 doi:10.1128/microbiolspec.MBP-0010-2014
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Image of FIGURE 2
FIGURE 2

In the presence of β-glucosides, the sugar is taken up by the β-glucoside permease of the PTS and concomitantly phosphorylated. The phosphoryl group is derived from phosphoenolpyruvate (PEP) and transferred via the phosphocarriers Enzyme I (EI) and HPr to the EIIB component of the β-glucoside permease. Under these conditions, the transcription-antiterminator protein BglG binds a stem-loop structure of the mRNA, thereby preventing the formation of a terminator structure, and the transcription of the mRNA can continue. Inactivation of the antiterminator protein BglG occurs in the absence of β-glucosides. BglG receives a phosphoryl goup from the β-glucoside permease and is now unable to bind the mRNA. The formation of a termination structure occurs and the transcription of the operon is aborted. Pyr, pyruvate. doi:10.1128/microbiolspec.MBP-0010-2014.f2

Source: microbiolspec July 2015 vol. 3 no. 4 doi:10.1128/microbiolspec.MBP-0010-2014
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Image of FIGURE 3
FIGURE 3

In the presence of cysteine, the acetyltransferase CysE is inhibited and the -acetyl-serine (OAS)-thiol-lyase CysK forms a complex with the transcription factor CymR. The protein complex binds to the CymR-regulated genes and prevents transcription. At low cysteine levels, the OAS-thiol-lyase converts serine and acetyl-CoA to OAS, which serves as the substrate for CysK to produce cysteine. doi:10.1128/microbiolspec.MBP-0010-2014.f3

Source: microbiolspec July 2015 vol. 3 no. 4 doi:10.1128/microbiolspec.MBP-0010-2014
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Image of FIGURE 4
FIGURE 4

Conventional enzymes (E), such as the β-galactosidase LacZ, catalyze metabolic reactions without controlling gene expression through modulating the activity of a transcription factor (TF). Bifunctional trigger enzymes (TEs) such as the glutamate dehydrogenase (GDH) from can control the activity of TFs by a direct protein-protein interaction. It has been suggested that the metabolites that are converted by the GDH also directly modulate the activity of the GDH-controlled TF, GltC. TEs like the glutamine synthetase (GS) from control the activities of TFs that do not response to metabolites. TFs such as the trifunctional PutA enzyme may have acquired a DNA-binding motif, which allows the enzyme to regulate gene expression depending of the metabolic state of the cell. TFs like BzdR from may be composed of a DNA-binding domain and an enzymatic domain that has lost its catalytic activity during evolution. These TE sense metabolites without converting them. S, substrate; P, product. doi:10.1128/microbiolspec.MBP-0010-2014.f4

Source: microbiolspec July 2015 vol. 3 no. 4 doi:10.1128/microbiolspec.MBP-0010-2014
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Tables

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TABLE 1

A compilation of trigger enzymes in bacteria

Source: microbiolspec July 2015 vol. 3 no. 4 doi:10.1128/microbiolspec.MBP-0010-2014

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