Role of OB-Fold Protein YdeI in Stress Response and Virulence of Salmonella enterica Serovar Enteritidis.
Aryashree ArunimaSunil Kumar SwainSaumya Darshana PatraSusmita DasNirmal Kumar MohakudNamrata MisraMrutyunjay SuarPublished in: Journal of bacteriology (2020)
An essential feature of the pathogenesis of the Salmonella enterica serovar Enteritidis wild type (WT) is its ability to survive under diverse microenvironmental stress conditions, such as encountering antimicrobial peptides (AMPs) or glucose and micronutrient starvation. These stress factors trigger virulence genes carried on Salmonella pathogenicity islands (SPIs) and determine the efficiency of enteric infection. Although the oligosaccharide/oligonucleotide binding-fold (OB-fold) family of proteins has been identified as an important stress response and virulence determinant, functional information on members of this family is currently limited. In this study, we decipher the role of YdeI, which belongs to OB-fold family of proteins, in stress response and virulence of S Enteritidis. When ydeI was deleted, the ΔydeI mutant showed reduced survival during exposure to AMPs or glucose and Mg2+ starvation stress compared to the WT. Green fluorescent protein (GFP) reporter and quantitative real-time PCR (qRT-PCR) assays showed ydeI was transcriptionally regulated by PhoP, which is a major regulator of stress and virulence. Furthermore, the ΔydeI mutant displayed ∼89% reduced invasion into HCT116 cells, ∼15-fold-reduced intramacrophage survival, and downregulation of several SPI-1 and SPI-2 genes encoding the type 3 secretion system apparatus and effector proteins. The mutant showed attenuated virulence compared to the WT, confirmed by its reduced bacterial counts in feces, mesenteric lymph node (mLN), spleen, and liver of C57BL/6 mice. qRT-PCR analyses of the ΔydeI mutant displayed differential expression of 45 PhoP-regulated genes, which were majorly involved in metabolism, transport, membrane remodeling, and drug resistance under different stress conditions. YdeI is, therefore, an important protein that modulates S Enteritidis virulence and adaptation to stress during infection.IMPORTANCE S Enteritidis during its life cycle encounters diverse stress factors inside the host. These intracellular conditions allow activation of specialized secretion systems to cause infection. We report a conserved membrane protein, YdeI, and elucidate its role in protection against various intracellular stress conditions. A key aspect of the study of a pathogen's stress response mechanism is its clinical relevance during host-pathogen interaction. Bacterial adaptation to stress plays a vital role in evolution of a pathogen's resistance to therapeutic agents. Therefore, investigation of the role of YdeI is vital for understanding the molecular basis of regulation of Salmonella pathogenesis. In conclusion, our findings may contribute to finding potential targets to develop new intervention strategies for treatment and prevention of enteric diseases.
Keyphrases
- escherichia coli
- pseudomonas aeruginosa
- staphylococcus aureus
- wild type
- biofilm formation
- antimicrobial resistance
- lymph node
- transcription factor
- genome wide
- cystic fibrosis
- type diabetes
- healthcare
- real time pcr
- palliative care
- oxidative stress
- protein protein
- gene expression
- early stage
- high resolution
- cell proliferation
- dendritic cells
- pi k akt
- life cycle
- social media
- adipose tissue
- single molecule
- cell migration
- reactive oxygen species
- immune response
- amino acid
- small molecule
- human health
- blood glucose
- cell cycle arrest
- genome wide identification
- high throughput
- label free