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Leucine-responsive regulatory protein (Lrp) acts as a virulence repressor in Salmonella enterica serovar Typhimurium.
J Bacteriol. 2009 Feb; 191(4):1278-92.JB

Abstract

Leucine-responsive regulatory protein (Lrp) is a global gene regulator that influences expression of a large number of genes including virulence-related genes in Escherichia coli and Salmonella. No systematic studies examining the regulation of virulence genes by Lrp have been reported in Salmonella. We report here that constitutive expression of Lrp [lrp(Con)] dramatically attenuates Salmonella virulence while an lrp deletion (Deltalrp) mutation enhances virulence. The lrp(Con) mutant caused pleiotropic effects that include defects in invasion, cytotoxicity, and colonization, whereas the Deltalrp mutant was more proficient at these activities than the wild-type strain. We present evidence that Lrp represses transcription of key virulence regulator genes--hilA, invF, and ssrA--in Salmonella pathogenicity island 1 (SPI-1) and 2 (SPI-2), by binding directly to their promoter regions, P(hilA), P(invF), and P(ssrA). In addition, Western blot analysis showed that the expression of the SPI-1 effector SipA was reduced in the lrp(Con) mutant and enhanced in the Deltalrp mutant. Computational analysis revealed putative Lrp-binding consensus DNA motifs located in P(hilA), P(invF), and P(ssrA). These results suggest that Lrp binds to the consensus motifs and modulates expression of the linked genes. The presence of leucine enhanced Lrp binding to P(invF) in vitro and the addition of leucine to growth medium decreased the level of invF transcription. However, leucine had no effect on expression of hilA and ssrA or on cellular levels of Lrp. In addition, Lrp appears to be an antivirulence gene, since the deletion mutant showed enhanced cell invasion, cytotoxicity, and hypervirulence in BALB/c mice.

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Authors+Show Affiliations

Baek CH
The Biodesign Institute, Arizona State University, P.O. Box 875401, 1001 S. McAllister Ave., Tempe, AZ 85287-5401, USA.
Wang S
No affiliation info available
Roland KL
No affiliation info available
Curtiss R
No affiliation info available

MeSH

AnimalsBacterial ProteinsCell LineEpithelial CellsGene Expression Regulation, BacterialLeucine-Responsive Regulatory ProteinMacrophagesMiceMice, Inbred BALB CMutationSalmonella InfectionsSalmonella typhimuriumTranscription, GeneticVirulence

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19074398

Citation

Baek, Chang-Ho, et al. "Leucine-responsive Regulatory Protein (Lrp) Acts as a Virulence Repressor in Salmonella Enterica Serovar Typhimurium." Journal of Bacteriology, vol. 191, no. 4, 2009, pp. 1278-92.
Baek CH, Wang S, Roland KL, et al. Leucine-responsive regulatory protein (Lrp) acts as a virulence repressor in Salmonella enterica serovar Typhimurium. J Bacteriol. 2009;191(4):1278-92.
Baek, C. H., Wang, S., Roland, K. L., & Curtiss, R. (2009). Leucine-responsive regulatory protein (Lrp) acts as a virulence repressor in Salmonella enterica serovar Typhimurium. Journal of Bacteriology, 191(4), 1278-92. https://doi.org/10.1128/JB.01142-08
Baek CH, et al. Leucine-responsive Regulatory Protein (Lrp) Acts as a Virulence Repressor in Salmonella Enterica Serovar Typhimurium. J Bacteriol. 2009;191(4):1278-92. PubMed PMID: 19074398.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Leucine-responsive regulatory protein (Lrp) acts as a virulence repressor in Salmonella enterica serovar Typhimurium. AU - Baek,Chang-Ho, AU - Wang,Shifeng, AU - Roland,Kenneth L, AU - Curtiss,Roy,3rd Y1 - 2008/12/12/ PY - 2008/12/17/entrez PY - 2008/12/17/pubmed PY - 2009/2/28/medline SP - 1278 EP - 92 JF - Journal of bacteriology JO - J Bacteriol VL - 191 IS - 4 N2 - Leucine-responsive regulatory protein (Lrp) is a global gene regulator that influences expression of a large number of genes including virulence-related genes in Escherichia coli and Salmonella. No systematic studies examining the regulation of virulence genes by Lrp have been reported in Salmonella. We report here that constitutive expression of Lrp [lrp(Con)] dramatically attenuates Salmonella virulence while an lrp deletion (Deltalrp) mutation enhances virulence. The lrp(Con) mutant caused pleiotropic effects that include defects in invasion, cytotoxicity, and colonization, whereas the Deltalrp mutant was more proficient at these activities than the wild-type strain. We present evidence that Lrp represses transcription of key virulence regulator genes--hilA, invF, and ssrA--in Salmonella pathogenicity island 1 (SPI-1) and 2 (SPI-2), by binding directly to their promoter regions, P(hilA), P(invF), and P(ssrA). In addition, Western blot analysis showed that the expression of the SPI-1 effector SipA was reduced in the lrp(Con) mutant and enhanced in the Deltalrp mutant. Computational analysis revealed putative Lrp-binding consensus DNA motifs located in P(hilA), P(invF), and P(ssrA). These results suggest that Lrp binds to the consensus motifs and modulates expression of the linked genes. The presence of leucine enhanced Lrp binding to P(invF) in vitro and the addition of leucine to growth medium decreased the level of invF transcription. However, leucine had no effect on expression of hilA and ssrA or on cellular levels of Lrp. In addition, Lrp appears to be an antivirulence gene, since the deletion mutant showed enhanced cell invasion, cytotoxicity, and hypervirulence in BALB/c mice. SN - 1098-5530 UR - https://www.unboundmedicine.com/medline/citation/19074398/Leucine_responsive_regulatory_protein__Lrp__acts_as_a_virulence_repressor_in_Salmonella_enterica_serovar_Typhimurium_ L2 - https://journals.asm.org/doi/10.1128/JB.01142-08?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -