The long-term goal of this laboratory is to better understand the molecular mechanisms of staphylococcal pathogenesis. Staphylococci are a group of bacteria most commonly causing nosocomial infections, many of which are life-threatening. These bacteria are also excellent in adapting to their environments. As a result, the emergence of antibiotic resistance strains in response to antibiotic usage has caused serious problems for controlling staphylococcal infections. Among all staphylococci, S. aureus is the most virulent species. This organism is capable of producing a plethora of virulence factors reflecting its ability to cause a wide range of human and animal diseases ranging from superficial skin infections to debilitating systemic infections. These virulence factors have been shown to be highly regulated by a complex regulatory network. In our laboratory, we have specifically focused on understanding regulation of virulence factors. We have taken an approach in which we used capsule as a target virulence factor to study virulence regulation. As all regulators can be tied together with respect to one specific target, our approach has resulted in an integrated networking model. Capsule endows S. aureus the ability to evade the host immune system, but it also blocks bacterial surface molecules from interacting with host environment during infection. Capsule thus is highly regulated and more than 29 regulators have been shown to affect capsule production. Among the regulators are major regulators such as Agr, MgrA and Sae, as well as unconventional regulator such as ClpC. To date, we have constructed a capsule regulatory network with 18 regulators. Recently, we have extended our efforts to study regulation of a-toxin, a well-studied toxin in S. aureus. Our current efforts are directed toward studying regulatory networking in vivo and investigating detailed mechanisms of regulation. Current projects include ClpC regulation of Agr and SigB using structural biology and mutational analysis approaches, as well as virulence regulation by small RNA. In addition, our laboratory is involved in staphylococcal biofilm studies. The ability to form biofilm has been shown to be crucial for staphylococci in device-related infections and other diseases such as osteomyelitis and endocarditis. We are interested in studying how biofilm is regulated and the mechanism of biofilm formation.
- M.G. Lei and C.Y. Lee. 2020. MgrA Activates Staphylococcal Capsule via SigA-Dependent Promoter. J Bacteriol. 203(2):e00495-20.
- M. G. Lei, D. D. Gudeta and C. Y. Lee. 2019. MgrA negatively impacts Staphylococcus aureusinvasion by regulating capsule and FnbA. Infection and Immunity. 87:e00590-19.
- D. D. Gudeta, M. G. Lei and C. Y. Lee. 2019. Contribution of hla regulation by SaeR to S. aureusUSA300 pathogenesis. Infection and Immunity. 87:e00231-19.
- M. G Lei and C. Y. Lee. 2018. Repression of capsule production by XdrA and CodY inStaphylococcus aureus. J. Bacteriol. 200(18):e00203-18.
- M. G. Lei*, R. K. Gupta*, and C. Y. Lee. 2017. Proteomics of Staphylococcus aureus biofilm matrix in a rat model of orthopedic implant-associated infection. PloS One, 12:e0187981 (*contribute equally).
- R. K. Gupta, T. T. Luong, and C. Y. Lee. 2015. Staphylococcus aureus RNAIII activates transcriptional regulator MgrA by mRNA stabilization. Proc. Natl. Acad. Sci. 112:14036-41. doi: 10.1073/pnas.1509251112. PMID: 26504242
- M. G. Lei and C. Y. Lee. 2015. RbsR activates capsule by represses rbsUDk operon in Staphylococcus aureus. J. Bacteriol. 197(23):3666-75. doi: 10.1128/JB.00640-15. PMID: 26350136.
Dr. Lee’s publications on PubMed.