Joined the Department in 2019
- B.S. in Biotechnology, Elizabethtown College. 2008
- Ph.D. in Microbiology and Immunology, University of North Carolina at Chapel Hill. 2013
- Postdoctoral Research Associate Princeton University, Department of Molecular Biology. 2014-19
- American Association for the Advancement of Science
- American Society for Microbiology
- American Society for Virology
The outer layer of the gram-negative bacterial cellular envelope contains an outer membrane (OM), which surrounds the bacteria and protects it from the environment. The OM is largely impermeable to both large and hydrophobic molecules, leading to the intrinsic resistance of gram-negative bacteria to many antibiotics. In fact, this makes gram-negative bacteria inherently orders of magnitude more resistant to many antibiotics than gram-positive bacteria. Due to this permeability barrier, the last new class of antibiotics treating gram-negative infections was developed in the 1960’s.
Given the importance of the OM for antibiotic resistance, it is imperative to clarify the mechanisms of OM maintenance and adaptation during stress. The overarching goal of my lab is to understand the mechanisms that strengthen the outer membrane (OM) permeability barrier of gram-negative bacteria during stress. The lab’s general approach is to use genetics and biochemistry to interrogate (i) changes to the barrier during stress, (ii) the mechanisms that strengthen the barrier, and (iii) the role of these changes in antibiotic resistance and pathogenesis.
Please visit the Mitchell Lab website for more information about the lab and our current projects.
- Grimm, J, Shi, H, Wang, W, Mitchell, AM, Wingreen, NS, Huang, KC et al.. The inner membrane protein YhdP modulates the rate of anterograde phospholipid flow in Escherichia coli. Proc Natl Acad Sci U S A. 2020;117 (43):26907-26914. doi: 10.1073/pnas.2015556117. PubMed PMID:33046656 PubMed Central PMC7604412.
- Hart, EM, Mitchell, AM, Konovalova, A, Grabowicz, M, Sheng, J, Han, X et al.. A small-molecule inhibitor of BamA impervious to efflux and the outer membrane permeability barrier. Proc Natl Acad Sci U S A. 2019;116 (43):21748-21757. doi: 10.1073/pnas.1912345116. PubMed PMID:31591200 PubMed Central PMC6815139.
- Mitchell, AM, Silhavy, TJ. Envelope stress responses: balancing damage repair and toxicity. Nat Rev Microbiol. 2019;17 (7):417-428. doi: 10.1038/s41579-019-0199-0. PubMed PMID:31150012 PubMed Central PMC6596312.
- May, KL, Lehman, KM, Mitchell, AM, Grabowicz, M. A Stress Response Monitoring Lipoprotein Trafficking to the Outer Membrane. mBio. 2019;10 (3):. doi: 10.1128/mBio.00618-19. PubMed PMID:31138744 PubMed Central PMC6538781.
- Silhavy, TJ, Mitchell, AM. Genetic Analysis of Protein Translocation. Protein J. 2019;38 (3):217-228. doi: 10.1007/s10930-019-09813-y. PubMed PMID:30684070 PubMed Central PMC6589372.
- Mitchell, AM, Srikumar, T, Silhavy, TJ. Cyclic Enterobacterial Common Antigen Maintains the Outer Membrane Permeability Barrier of Escherichia coli in a Manner Controlled by YhdP. mBio. 2018;9 (4):. doi: 10.1128/mBio.01321-18. PubMed PMID:30087168 PubMed Central PMC6083912.
- Mitchell, AM, Wang, W, Silhavy, TJ. Novel RpoS-Dependent Mechanisms Strengthen the Envelope Permeability Barrier during Stationary Phase. J Bacteriol. 2017;199 (2):. doi: 10.1128/JB.00708-16. PubMed PMID:27821607 PubMed Central PMC5198486.
- Konovalova, A, Mitchell, AM, Silhavy, TJ. A lipoprotein/β-barrel complex monitors lipopolysaccharide integrity transducing information across the outer membrane. Elife. 2016;5 :. doi: 10.7554/eLife.15276. PubMed PMID:27282389 PubMed Central PMC4942254.
- Xiao PJ, Mitchell AM, Haung L, Li C, & Samulski RJ. (2016) Disruption of microtubules post virus entry enhances adeno-associated virus vector transduction. Human Gene Therapy. 27(4): 309-24.
- Mitchell AM, Moser R, Samulski RJ, & Hirsch ML. (2016) Stimulation of AAV gene editing via DSB repair. In Hirsch ML, Cathomen T, & Porteus MH (Eds.), Genome Editing: The Next Step in Gene Therapy (pgs. 125-137). ISBN: 978-1-4939-3507-9.
- Vance MA, Mitchell AM, & Samulski RJ. (2015) rAAV biology, infectivity and therapeutic use from bench to clinic. In Hashad ID (Ed.), Gene Therapy. ISBN: 978-953-51-4380-2
- Mitchell AM, Hirsch ML, Li C, & Samulski RJ. (2014) The promyelocytic leukemia protein is a cell-intrinsic defense factor inhibiting parvovirus DNA replication. Journal of Virology. 88(2): 925-36.