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Biography

"Yinduo Ji is an Associate Professor of microbiology at the University of Minnesota, USA. He obtained his Ph.D. from the Chinese Center for Disease Control and Prevention in 1993 and did his postdoctoral training at the University of Minnesota Medical School from 1994 -1997. Then, he joined in the GlaxoSmithKline Pharmaceuticals Research & Development, USA, and performed basic anti-infective drug discovery. Since 2002, he has joined in the Department of Veterinary Biomedical Science at the University of Minnesota as a faculty member; his research focuses on the functional genomics, molecular and cellular pathogenesis of Staphylococcus aureus, and antibacterial drug discovery."

Abstract

"Staphylococcus aureus is a major human and animal pathogen that can cause a variety of diseases. The exported α-toxin (hla) is an important virulence factor in many S. aureus infections. Although the complicated regulation of hla expression has been well studied in human S. aureus isolates, the mechanisms of hla regulation in bovine S. aureus isolates remain poorly defined. We found that many bovine S. aureus isolates generate tremendous amounts of the toxin in vitro culture compared to human clinical S. aureus isolates. To explore potential regulatory mechanisms, we identified predominant single nucleotide polymorphisms (SNPs) at the hla promoter regions. Using bioinformatics, site-directed mutagenesis and hla promoter-lux reporter approaches, we identified and demonstrated that the SNPs contribute to the differential control of hla expression among bovine and human S. aureus isolates. Using a DNA affinity assay, gel-shift assays and a null mutant, we identified and revealed that an hla positive regulator, SarZ, mainly contributes to the involvement of the SNPs in mediating hla expression. In addition, we found that the hyper-production of α-toxin in these bovine S. aureus isolates may be partially attributable to higher transcription levels of hla positive regulators, including agrA, saeR, and arlR, but a lower expression level of hla repressor rot compared to the human S.aureus isolate. These findings provide new insights into the regulatory mechanisms of hla expression in S. aureus. Moreover, the identification of predominant SNPs in the hla promoter region may provide a novel method for genotyping the S. aureus isolates."

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