The Subtleties and Contrasts of the LeuO Regulator in Salmonella Typhi: Implications in the Immune Response

Abstract

Salmonella are facultative intracellular pathogens. Salmonella infection occurs mainly by expression of two Salmonella pathogenicity Islands (SPI-1 and SPI-2). SPI-1 encodes transcriptional factors that participate in the expression of virulence factors encoded in the island. However, there are transcriptional factors encoded outside the island that also participate in the expression of SPI-1-encoded genes. Upon infection, bacteria are capable of avoiding the host immune response with several strategies that involve several virulence factors under the control of transcriptional regulators. Interestingly, LeuO a transcriptional global regulator which is encoded outside of any SPI, is proposed to be part of a complex regulatory network that involves expression of several genes that help bacteria to survive stress conditions and, also, induces the expression of porins that have been shown to be immunogens and can thus be considered as antigenic candidates for acellular vaccines. Hence, the understanding of the LeuO regulon implies a role of bacterial genetic regulation in determining the host immune response.

CRISPR-cas3 of Salmonella Upregulates Bacterial Biofilm Formation and Virulence to Host Cells by Targeting Quorum-Sensing Systems

“…Additionally, studies found that cse1 from this bacterium was expressed in specific growth condition (N-minimal medium) [27], which promoted the expression of the Salmonella pathogenicity island 2 genes [28]. Furthermore, the S. Typhi CRISPR-Cas locus is regulated by LeuO (LysR-type regulator), H-NS (heat-stable nucleoid-structuring protein), and LRP (leucine-responsive regulatory protein) [27,29], which are involved in pathogenesis [30][31][32][33][34][35]. The cas genes of the type I-C CRISPR-Cas system in Myxococcus xanthus seem to be strongly embedded within the regulatory circuits that control the fruiting-body formation process and are tightly regulated by various intercellular quorum-sensing (QS) signals and intracellular signaling cascades [36,37].…”

Salmonella enterica serovar Typhi genomic regions involved in low pH resistance and in invasion and replication in human macrophages

“…Since LeuO is the only global transcriptional regulator coded in the 25 kb deleted fragment of S. Typhi ΔF4, and LeuO is involved in different biological processes including detoxification, virulence, porin synthesis, and regulation of the CRISPR-Cas system in E. coli and Salmonella (De la Cruz et al 2007;Dillon et al 2012;Espinosa and Casadesús 2014;Guadarrama et al 2014;Hernández-Lucas et al 2008;Medina-Aparicio et al 2011;Westra et al 2010), a leuO mutant was obtained. Interestingly, the S. Typhi ΔF4 also lacks genes involved in thiamine transport (thiQP-tbpA).…”

Multi-Factor Regulation of the Master Modulator LeuO for the Cyclic-(Phe-Pro) Signaling Pathway in Vibrio vulnificus

“…Members of this family have been identified in many bacteria, including enteric pathogens such as Escherichia coli, Salmonella enterica serovar Typhimurium, Enterobacter cloacae , and Vibrio spp 23 . LeuO regulates a wide variety of genes that are involved in amino acid biosynthesis, catabolism of aromatic compounds, antibiotic resistance, nitrogen fixation, oxidative stress response, quorum sensing, and virulence 24–27 . The structure of LTTR proteins includes an N-terminal DNA-binding helix-turn-helix motif and a C-terminal co-inducer-binding domain 23,28 .…”