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YIXIN SHI Assistant Professor Ph. D., 2000 Kyushu University, Japan Phone: (480) 965-3904 Send e-mail to yixin.shi@asu.edu

Mechanisms of Salmonella resistance to antimicrobial peptides

Our research group works on genetic analysis of virulence determinants in enteric bacterium Salmonella typhimurium, specifically we are interested in molecular mechanisms of resistance to host innate immune component called antimicrobial peptides. In this regard, we study gene regulation involved in bacterial survival in host hostile environments, and investigate specific gene functions. Our research goal is to answer following questions: 1) Which bacterial gene responds to host intracellular signals and confers resistance to specific antimicrobial peptide in Salmonella typhimurium. 2) Identify gene profile and their regulations responsible for resistance to antimicrobial peptides adapted to different structures in Salmonella. 3) Characterize mechanisms for resistance to specific antimicrobial peptide in Salmonella typhimurium and other enteric bacteria.

We are interested in covalent modifications of bacterial outer membrane component lipopolysaccharide (LPS) directed by the two-component regulatory systems including PhoP/PhoQ and PmrA/PmrB, which sense extracytoplasmic stimuli to allow the bacteria to respond to different environments and confer resistance to various antimicrobial peptides. Specifically our research group studies temporal expression patterns for different modifying enzymes in this inducible process.

Homeostasis of metal ions in enteric bacteria

We focus on post-transcriptional regulation of magnesium homeostasis of enteric pathogenic bacteria in in vitro growth and within host environments. Our group studies following issues: 1) How does Salmonella build up magnesium homeostasis? 2) How does Mg²⁺ concentration affect homeostasis of other divalent metal ions in Salmonella? 3) How is a metal ion homeostasis regulated and what is the function in Salmonella infection?

In our laboratory, we perform experiments on genetic analysis of gene regulation and biochemical approaches to gene function including one step gene inactivation, chromosomal site-directed mutagenesis, assay for enzymatic activities, DNase I footprinting assay, S1 mapping, western blot, and the enzymatic and chemical mapping for RNA structure, etc..

Selected Publications

Shi Y, Latifi T, Cromie MJ, Groisman EA. 2004 Transcriptional control of the antimicrobial peptide resistance ugtL gene by the Salmonella PhoP and SlyA regulatory proteins. J Biol Chem. 279(37):38618-25.

Shi Y, Cromie MJ, Hsu FF, Turk J, Groisman EA. 2004 PhoP-regulated Salmonella resistance to the antimicrobial peptides magainin 2 and polymyxin B. Mol. Microbiol. 53(1):229-41.

Shi Y, Kong W, Nakayama K. 2000 Human lactoferrin binds and removes the hemoglobin receptor protein of the periodontopathogen Porphyromonas gingivalis. J Biol. Chem. 275(39):30002-8.

Shi Y, Ratnayake DB, Okamoto K, Abe N, Yamamoto K, Nakayama K 1999 Genetic analyses of proteolysis, hemoglobin binding, and hemagglutination of Porphyromonas gingivalis. Construction of mutants with a combination of rgpA, rgpB, kgp, and hagA. J Biol. Chem. 274(25):17955-60.