Bacterial Physiology and Antibiotic Action
Regulation of Mycobacterial Growth
Mycobacteria are phylogenetically distinct from the model organisms classically used to study prokaryotic cell biology. Consequently, the mechanisms controlling the growth, division, and morphogenesis of the mycobacterial cell are unique to this genus. We are using genetics, time-lapse microscopy, and high-throughput image-based screening to understand the mechanisms regulating these processes (for more information see a commentary on our work).
 Dynamic reorganization of cell wall regulatory complexes |
 Sequential recruitment of cell wall synthetic and regulatory complexes to the developing septum |
 Dynamics of arabinogalactan synthesis during growth |
 Differential sorting of polar and septal cell wall regulatory complexes |
 Morphology mutants of M. smegmatis |
Dormancy and Antibiotic Action
M. tuberculosis responds to the stress of host immunity by slowing its growth and metabolic rate. This response renders the bacterium tolerant to both immune effectors and antibiotic treatment. Using a combination of genetic and metabolomic approaches, we seek to understand the physiological state of these quiescent cells and design new strategies to improve antibiotic efficacy.
Rittershaus ES, Baek SH, Sassetti CM. The normalcy of dormancy: common themes in microbial quiescence. Cell Host Microbe. 2013 Jun 12; 13(6):643-51. PMID: 23768489
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Alterations in metabolite pools |
Rittershaus, ESC Baek, SH, Krieger, IV, Nelson, SJ,Cheng, YS, Nambi, S, Baker, RE, Leszyk, JD, Shaffer, SA, Sacchettini, JS, Sassetti, CM. A lysine acetyltransferase contributes to the metabolic adaptation to hypoxia inMycobacterium tuberculosis. Cell Chem Bio. Cell chem bio. 25, 1–11, 2018
