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.
Highlights
Successful defence against extracellular and intracellular bacteria primarily relies on the ability of innate immune cells to sense present bacteria followed by activation of the adequate matching immune response
The most prominent pathways involved are mediated by mitogen-activated protein kinases (MAPKs) or nuclear factor-κB (NF-κB), which are initiated by path-specific adapter proteins and transferred by downstream phosphorylation cascades [3]
All pathways can synergize to guarantee a specific and appropriate immune response for the present pathogen. This is enabled by the high diversity of pathogen recognition receptors (PRRs), pathogen-associated molecular patterns (PAMPs) and PRR adapter proteins and their numerous ways to be combined during innate immune response [1,4]
Summary
Successful defence against extracellular and intracellular bacteria primarily relies on the ability of innate immune cells to sense present bacteria followed by activation of the adequate matching immune response. The long ncRNAs (lncRNAs) as well as some classes of short ncRNAs are involved in epigenetic regulations but its most studied group, the miRNAs (microRNA), are mostly involved in RNA destruction [8] Another point for interference with gene expression is during processing of mRNAs, which includes 5 capping, alternative splicing and polyadenylation [9,10]. These structures are crucial for translation initiation and can gain enough time for the mRNA to be translated This represents a further step for interference with gene expression, as there is the need of several factors to induce and prolong translation [14]. Bacteria express several virulence factors, the so-called effectors These proteins are able to mimic host enzymes, thereby manipulating the host response following invasion favouring intracellular survival, persistence and spreading. In the following we will present an overview on the manipulation of host gene expression at different levels by nucleomodulins and other bacterial effectors
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