Small Non-Coding RNAs in Salmonella–Host Interactions: History
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Salmonella species infect hosts by entering phagocytic and non-phagocytic cells, causing diverse disease symptoms, such as fever, gastroenteritis, and even death. Therefore, Salmonella has attracted much attention. Many factors are involved in pathogenesis, for example, the capsule, enterotoxins, Salmonella pathogenicity islands (SPIs), and corresponding regulators. These factors are all traditional proteins associated with virulence and regulation. Recently, small non-coding RNAs (sRNAs) have also been reported to function as critical regulators. Salmonella has become a model organism for studying sRNAs. sRNAs regulate gene expression by imperfect base-pairing with targets at the post-transcriptional level. sRNAs are involved in diverse biological processes, such as virulence, substance metabolism, and adaptation to stress environments. 

  • sRNAs
  • Salmonella
  • host
  • interactions

1. Introduction

Salmonella enterica is one of the leading causes of foodborne gastroenteritis worldwide. The two most important serovars of Salmonella are Salmonella enterica serovar Typhimurium (S. Typhimurium) and Salmonella enterica serovar Enteritidis (S. Enteritidis), which cause non-typhoid salmonellosis infections [1]. As an intracellular zoonotic pathogen, Salmonella regularly infects hosts. It enters the stomach and intestinal lumen of the host after ingestion of contaminated food, causing gastroenteritis in both humans and animals as well as typhoid fever in mice. Salmonella must survive within the acidic environment of the stomach and penetrates the gut barrier via M cells in Peyer’s patches of the intestine [2]. Salmonella invades the cell membrane and forms Salmonella-containing vacuoles (SCVs) with the help of a Type III secretion system (T3SS) encoded by Salmonella pathogenicity islands (SPIs) [3]. After that, macrophages engulf the bacteria and kill them to resist infection by producing reactive nitrogen species (RNS) and reactive oxygen species (ROS) [4]. Interestingly, Salmonella employs sophisticated strategies to survive and replicate inside phagocytic and non-phagocytic cells, causing serious diseases in humans and animals.
The small non-coding RNAs (sRNAs), which are known to be involved in the regulation of gene expression, have a length of 50–500 nucleotides and have been found in various bacteria, for example, Escherichia coliListeria monocytogenes, and S. Typhimurium [5,6]. Based on their mode of base-pairing, they are classified into cis- and trans-encoded sRNAs. Cis-encoded sRNAs are transcribed from the same loci as the mRNAs on the opposite strand of DNA and bind to their cognate mRNA targets with perfect complementarity, resulting in either transcriptional termination or translational initiation. Trans-encoded sRNAs interact with multiple mRNA targets through imperfect complementation [6,7]. Gene expression is usually regulated by trans-acting sRNAs at the post-transcriptional level [8]. The functions of more than half of the trans-acting sRNAs require the chaperone protein Hfq, which plays an important role in regulation by stabilizing sRNAs and mediates their interaction with the trans-encoded target mRNAs of host cells, leading to repression of translation or acceleration of mRNA decay [9]. S. Typhimurium expresses hundreds of sRNAs, many of which are activated under special stress and virulence conditions, suggesting that sRNAs are an important component of regulatory networks controlling gene expression in bacteria during host infection [10].
sRNAs regulate many physiological processes in bacteria, including metabolism, iron homeostasis, quorum sensing, outer membrane protein biosynthesis, and the regulation of virulence genes [11,12]. In recent years, attention has been focused on the functions of sRNAs in bacteria–host interactions. To establish a successful infection, Salmonella must first resist the acidic environment and oxidative stress, adhere to and invade non-phagocytic cells, and finally evade host immunity to survive inside macrophages [13]. sRNAs play integral roles in bacterial stress responses, promote intracellular survival, and modulate host immune responses [9,14]. In this review, we summarize the roles of sRNAs in the interaction between Salmonella and host cells (see Table 1 for a summary of sRNAs), aiming to understand the roles of sRNAs upon host cell infection, provide an overview of the functional mechanisms of sRNAs, and provide ideas to improve host resistance to Salmonella infection.

This entry is adapted from the peer-reviewed paper 10.3390/biology11091283

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