From Gene to Protein-How Bacterial Virulence Factors Manipulate Host Gene Expression During Infection

Abstract

Bacteria evolved many strategies to survive and persist within host cells. Secretion of bacterial effectors enables bacteria not only to enter the host cell but also to manipulate host gene expression to circumvent clearance by the host immune response. Some effectors were also shown to evade the nucleus to manipulate epigenetic processes as well as transcription and mRNA procession and are therefore classified as nucleomodulins. Others were shown to interfere downstream with gene expression at the level of mRNA stability, favoring either mRNA stabilization or mRNA degradation, translation or protein stability, including mechanisms of protein activation and degradation. Finally, manipulation of innate immune signaling and nutrient supply creates a replicative niche that enables bacterial intracellular persistence and survival. In this review, we want to highlight the divergent strategies applied by intracellular bacteria to evade host immune responses through subversion of host gene expression via bacterial effectors. Since these virulence proteins mimic host cell enzymes or own novel enzymatic functions, characterizing their properties could help to understand the complex interactions between host and pathogen during infections. Additionally, these insights could propose potential targets for medical therapy.

Keywords: bacteria; gene expression; host-pathogen interaction; immune response; inflammation; manipulation; persistence; replicative niche; virulence factors.

Figure 1

Steps of host gene expression manipulated by bacterial pathogens. The figure provides an overview over the main steps of gene expression that are indicated at the left side (I-VI). The numbers in the scheme highlight distinct characteristic processes that are part of each gene expression level and are listed in the legend at the right side. Different bacterial pathogens (indicated at the right) have been described to target the distinct steps and processes during host gene expression to their favor. For detailed information please refer to the text of this review.