INDIVIDUAL RESEARCHERGuangchun Bai , Ph.D. , M.D.
Education1991 - M.D. from Fourth Military Medical University, China
1999 - Ph.D. from Fourth Military Medical University, China
Our work focuses on bacterial gene regulation and pathogenesis. Currently we are interested in two pathogens, Mycobacterium tuberculosis and Streptococcus pneumoniae. The long-term objective of this laboratory is to better understand the molecular basis of these pathogens for establishing effective strategies of prevention and therapy. We generally employ multiple approaches including genetics, biochemistry, molecular biology and cellular biology to study these pathogens.
M. tuberculosis is the causative agent of tuberculosis, which has successfully infected about one-third of the world’s population. Although an attenuated vaccine, M. bovis BCG, was available almost a century ago and anti-tubercular drugs have been exploited for many decades, the current strategies are still inadequate to control the prevalence. For this pathogen, our primary interest focuses on how cyclic nucleotides, especially c-di-AMP and c-di-GMP, contribute to the bacterial pathogenesis at molecular and cellular levels. Additionally, we are also interested in screening compounds as potential anti-TB drugs to specifically block the bacterial metabolism pathways.
S. pneumoniae is a commensal of the human respiratory tract, but it can still cause a variety of infections, such as pneumonia, meningitis, otitis media and bacteremia. Although a plethora of virulence determinants have been recognized in this pathogen, it remains largely unknown about how metabolic pathways enable the pathogen to acquire nutrients and cause diseases. A recent genome-wide mutagenesis study mapped 169 pneumococcal genes that were essential in an otitis media model. These genes include two members in the bacterial arginine deiminase pathway, arcD and arcT. We are currently exploring the molecular mechanism of the attenuation by deletion of these arc genes.
- Bai G, Gazdik MA, Schaak DD, McDonough KA. The Mycobacterium bovis BCG cyclic AMP receptor-like protein is a functional DNA binding protein in vitro and in vivo, but its activity differs from that of its M. tuberculosis ortholog, Rv3676. Infect Immun. 2007 Nov;75(11):5509-17
- Bai G, Schaak DD, McDonough KA. cAMP levels within Mycobacterium tuberculosis and Mycobacterium bovis BCG increase upon infection of macrophages. FEMS Immunol Med Microbiol. 2009 Jan;55(1):68-73
- Bai G, Knapp GS, McDonough KA. Cyclic AMP signalling in mycobacteria: redirecting the conversation with a common currency. Cell Microbiol. 2011 Mar;13(3):349-58
- Bai G, Schaak DD, Smith EA, McDonough KA. Dysregulation of serine biosynthesis contributes to the growth defect of a Mycobacterium tuberculosis crp mutant. Mol Microbiol. 2011 Oct;82(1):180-98
- Bai Y, Yang J, Zhou X, Ding X, Eisele LE, Bai G. Mycobacterium tuberculosis Rv3586 (DacA) is a diadenylate cyclase that converts ATP or ADP into c-di-AMP. PLoS One. 2012;7(4):e35206