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 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 use capsule and α-toxin as target virulence factors to study virulence regulation. Capsule endows S. aureus the ability to evade the host immune system but also blocks bacterial surface molecules from interacting with host environment during infection. On the other hand, α-toxin is a major toxin produced by S. aureus, which is highly expressed in soft-tissue infections but much reduced during invasive infections. Both capsule and α-toxin are highly regulated. By studying their regulation, we aims to build an integrated regulatory model as well as to understand how virulence genes are differentially regulated. Our current efforts are directed toward studying regulatory networking in vivo and investigating mechanisms of regulation. Current projects include ClpC regulation of Agr and SigB using structural biology and mutational analysis approaches, as well as regulation of carriage to disease transition 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 serious 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. 2022. Regulation of Staphylococcal Capsule by SarZ is SigA-Dependent. J. Bacteriol. 204:e00152-22
- M. G. Lei, R. K. Gupta and C. Y. Lee. 2021. A Rat Model of Orthopedic Implant-Associated Infection for Identification of Staphylococcal Biofilm Proteins. In Staphylococcus aureus (pp. 117-125). Humana, New York, NY.
- 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 aureus invasion 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. aureus USA300 pathogenesis. Infection and Immunity. 87:e00231-19.
- M. G Lei and C. Y. Lee. 2018. Repression of capsule production by XdrA and CodY in Staphylococcus 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