Araceli E. Santiago, PhD|“Characterization of a large family of anti-activators accompanying XylS/AraC family regulatory proteins in pathogenic bacteria”

Date: Friday January 15, 2016
Time: 11:45 AM until 1:00 PM
Location: MR-4 second floor conf room

Research Description

AraC/Xyls family is a large family of transcriptional regulators in Gram-negative. 1,974 know and putative members of AraC/XylS family members have been identified in 149 bacteria genomes. Members of this family control metabolic, cellular stress, and bacterial pathogenesis.

We uncovered and characterized a new family of negative regulators (ANR) (AraC Negative Regulators) in Gram-negative bacteria. ANR factors suppress virulence genes by directly down-regulating AraC/XylS members in Gram-negative bacteria.

We performed iterative in silico genome searches using known ANR sequences. This analysis revealed at least 282 members of the ANR family distributed within the same genomes as AraC family members, spanning at least 26 distinct Gram-negative species including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., Enterotoxigenic (ETEC) and Enteroaggregative E. coli (EAEC), and members of the Pasteurellaceae. Members of the ANR family are small molecules (4.36-9.54 kDa), formed by 3 hypothetical helixes. Some of the ANR members characterized in our group include Aar (AggR activated regulator) in EAEC, Rnr (Rns negative regulator) in Citrobacter rodentium, Cnr-1 and Cnr-2 (CfaD negative regulator) in ETEC, ANR_Vibrio in Vibrio cholerae, and ANR_Salmonella in Salmonella enterica. Aar, in EAEC strain 042 down regulates AggR (member of AraC/XylS family), and 44 genes identified as part of the AggR regulon, including AAF fimbria, dispersin and its secretion system aat, and type VI secretion

Objective:

1. Molecular dissection of ANR’s role in pathogenesis
2. Explore the potential use of ANR in the treatment of enteropathogenic bacterial diseases.

Please RVSP to Wendy Cline – cline@virginia.edu (pizza served at 11:45 a.m.)