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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).

Video1

Dynamic reorganization of cell wall regulatory complexes

Video2

Sequential recruitment of cell wall synthetic and
regulatory complexes to the developing septum

Video3

Dynamics of arabinogalactan synthesis during growth
Video4

Differential sorting of polar and septal cell wall regulatory complexes
Video5

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

Dormancy and Antibiotic Action

Alterations in metabolite pools
upon exposure to growth-limiting stress

 

RittershausESC 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

 

 

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