About the Project
In this project, we will investigate the cell envelope stress sensing mechanisms of AmgS and its E. coli homologue, EnvZ. We will develop reporter strains for activation of the envelope stress response and determine conditions that activate it in Pseudomonas aeruginosa. We will also use genetic screens to identify additional genes contributing to the response . Finally, we will conduct biomolecular simulations of EnvZ in realistic membrane mixture models and construct a structural model of AmgS. Questions of interest will include: 1) how do EnvZ and AmgS interact with the cytoplasmic membrane and other proteins required for the response; 2) how might these interactions be perturbed by conditions that lead to activation of the sensor; and 3) how do specific downstream results of activation of the pathway contribute to antibiotic tolerance? A long-term objective is to gain insight toward defeating this bacterial mechanism for increasing tolerance of antibiotics.
 Lee et al., PNAS, 2009.
 Basta et al., mBio, 2017.
Recent work from the lab can be found in the following references:
Meirelles et al., bioRxiv, 2020; doi: 10.1101/2020.04.20.049437
Bergkessel, Current Opinion Microbiology, 2020; doi: 10.1016/j.mib.2020.07.010
Basta et al. mBio, 2017; doi: 10.1128/mBio.01170-17
Kopec et al., Nature Chemistry, 2018; doi: 10.1038/s41557-018-0105-9
Alghamdi et al., eLife, 2020; doi: 10.7554/elife.56416.sa2
Williamson et al., eLife, 2020; doi: 10.7554/eLife.57183
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