YaeB, Expressed in Response to the Acidic pH in Macrophages, Promotes Intracellular Replication and Virulence of Salmonella Typhimurium.

Huan Zhang,Runxia Lv,Shuangshuang Ma,Xiaorui Song,Peisheng Wang,Lingyan Jiang

doi:10.3390/ijms20184339

Huan Zhang, Runxia Lv + Show 4 more

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https://doi.org/10.3390/ijms20184339

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Abstract

Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that infects humans and animals. Survival and growth in host macrophages represents a crucial step for S. Typhimurium virulence. Many genes that are essential for S. Typhimurium proliferation in macrophages and associated with virulence are highly expressed during the intracellular lifecycle. yaeB, which encodes an RNA methyltransferase, is also upregulated during S. Typhimurium growth in macrophages. However, the involvement of YaeB in S. Typhimurium pathogenicity is still unclear. In this study, we investigated the role of YaeB in S. Typhimurium virulence. Deletion of yaeB significantly impaired S. Typhimurium growth in macrophages and virulence in mice. The effect of yaeB on pathogenicity was related to its activation of pstSCAB, a phosphate (Pi)-specific transport system that is verified here to be important for bacterial replication and virulence. Moreover, qRT-PCR data showed YaeB was induced by the acidic pH inside macrophages, and the acidic pH passed to YeaB through inhibiting global regulator histone-like nucleoid structuring (H-NS) which confirmed in this study can repress the expression of yaeB. Overall, these findings identified a new virulence regulatory network involving yaeB and provided valuable insights to the mechanisms through which acidic pH and low Pi regulate virulence.

Highlights

Typhimurium) is a significant food-borne pathogen that infects the intestinal epithelium via the Salmonella pathogenicity island (SPI)-1-encoded type 3 secretion system [1]
At 16 hpi, an average of 27 WT bacterial cells were found in infected cells, whereas the average number of ∆yaeB bacterial cells was 7
Consistent with the upregulation of yaeB, the expression of pstSCAB was highly induced (13.1–18.7-fold) by acidic pH (Figure 5C). These findings indicated that YaeB and Pi-specific transport (Pst) were upregulated in response to an acidic pH

Summary

Introduction

Typhimurium) is a significant food-borne pathogen that infects the intestinal epithelium via the Salmonella pathogenicity island (SPI)-1-encoded type 3 secretion system [1]. After passage through the intestinal epithelium, bacteria are incorporated mainly by macrophages [2]. The adaptation to host macrophages for growth is an essential step of S. Typhimurium pathogenesis, inducing systemic infections with fatal outcomes [3]. Typhimurium mostly resides within Salmonella-containing vacuoles (SCVs), which protects bacteria from killing by antimicrobial parasitic cell activities and facilitates bacterial survival and replication within macrophages [4]. SCV maturation is involved in acidification [5], preventing the generation of toxic free radicals, formation of Salmonella-induced filaments, resistance to antibacterial peptides and regulation of juxtanuclear positioning [6]. Typical characteristics of the mature SCV include high levels of K+; mildly acidic pH (5.5–4.9); low Mg2+, PO43−, and Fe2+ levels [7,8]; and freely available oxygen [9]

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