Petra Levin

Petra Levin

George William and Irene Koechig Freiberg Professor of Biology
Associate Chair of Faculty Research and Development
PhD, Harvard University
research interests:
  • Cell Growth
  • Cell Size
  • Cell Cycle Progression
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    contact info:

    mailing address:

    • Washington University
      CB 1137
      One Brookings Drive
      St. Louis, MO 63130-4899
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    Professor Levin's research interests include the temporal and spatial control of cell division, cell size control, and cell cycle dynamics in bacterial systems.

    The Levin Lab studies how cells respond to changes in the environment, specifically changes in the availability of essential nutrient, by altering their growth rate, cell shape, and composition. For example, the Levin Lab asks how cells “know” when they are starving for carbon and how they reduce growth rate and daughter cell production to compensate. Because nutrient starvation typically increases the ability of bacteria to survive in the presence of antibiotics, research in the Levin Lab’s will hopefully help us understand how human pathogens are so adept at acquiring antibiotic resistance, a growing crisis in today’s world. What is it about starving that makes cells more resistant to antibiotics and how can we influence this? 

    Research Interests

    Nutrients, cell growth, cell size, and cell cycle progression

    Nutrient availability is a primary determinant of cell size. Single-celled organisms cultured in nutrient-rich medium can be up to three times the size of their counterparts cultured under nutrient-poor conditions. Understanding the regulatory circuits and molecular mechanisms responsible for coordinating cell growth and cell size with nutrient availability and cell cycle progression is a primary objective of the lab.

    Environmental determinants of antibiotic resistance & tolerance

    Bacteria are exquisitely sensitive to their environment, displaying chameleon-like changes in growth rate and composition as they adapt to changes in nutrient availability, osmotic stress, and pH. Growth in nutrient-poor conditions leads to accumulation of the small molecule, guanosine tetraphosphate or ppGpp. A global inhibitor of biosynthesis, ppGpp is implicated in antibiotic tolerance and the development of persister cells that survive for long periods in the presence of bacteriocidal compounds.

    Taking advantage of our finding that drugs that inhibit fatty acid synthesis drive entry into a persister-like state, we are systematically identifying ppGpp-dependent mechanisms underlying tolerance to antibiotics targeting DNA replication, cell wall synthesis, and protein synthesis. Levin Lab is also investigating a newly identified link between environmental pH and resistance to cell wall active drugs.

    Spatial and Temporal Control of Cell Division

    In bacteria, cell division is initiated by the assembly of the tubulin-like cytoskeletal protein FtsZ into a ring-like structure at the future division site. The FtsZ ring serves as a scaffold for assembly of the division machinery and constricts at the leading edge of the invaginating septum during cytokinesis. Precisely orchestrated changes in FtsZ assembly dynamics ensure that bacterial cells divide in the right place and at the right time. However, the signals triggering FtsZ assembly at the onset of the cell cycle and driving FtsZ ring constriction at the end of the cell cycle remain elusive.  Identifying the regulatory factors coupling FtsZ assembly and division to cell growth and the cell cycle is a major focus of our research.

    Selected Publications

    Complete publications list

    Mueller, E. A., A. G. Iken‡, M. A. Oeztuerk, M. Winkle, M. Schmitz, W. Vollmer, B. Di Ventura, and P. A. Levin. (2021) The active repertoire of Escherichia coli peptidoglycan amidases varies with physiochemical environment, Mol. Microbiol., 116(1):311-328.  DOI: 10.1111/mmi.14711 (Available on bioRxiv https://doi.org/10.1101/2020.10.19.344754)

    Shi, H., C. S. Westfall, J. Kao, P. D. Odermatt, S. Cesar, M. Sievert, J. Moore, C. G. Gonzalez, L. Zhang, J. E. Elias, F. Chang, K. C. Huang, and P. A. Levin. (2021) Starvation induces shrinkage of the bacterial cytoplasm, PNAS 118 (24) e2104686118 DOI: 10.1073/pnas.2104686118 (Available on bioRxiv, https://doi.org/10.1101/2020.12.06.413849)

    Mueller, E. A, C. S. Westfall, and P. A. Levin. (2020) Environmental pH impacts division assembly and cell size in Escherichia coli, PLOS Genetics, 16(3): e1008685. https://doi.org/10.1371/journal.pgen.1008685. PMID: 32203516

    Cohan, M. C., Anna M. P. Eddelbuettel, P. A. Levin, and R. V. Pappu. (2020) Dissecting the functional contributions of the intrinsically disordered C-terminal tail of B. subtilis FtsZ, Journal of Molecular Biology. https://doi.org/10.1016/j.jmb.2020.03.008; PMID: 32198113

    Fernández-Coll, L., M. Maciag-Dorszynska, K. Tailor, S. Vadia, P. A. Levin, A. Szalewska-Palasz, and M. Cashel. (2020) The absence of (p)ppGpp renders initiation of Escherichia coli chromosomal DNA synthesis independent of growth rates, mBio, 11 (2) e03223-19; DOI: 10.1128/mBio.03223-19; PMID: 32156825

    Haeusser, D. P. and P. A. Levin (2019) Keeping Replication on Par with Division in Bacillus, Mol Microbiol, 112:747-750. Invited Commentary. DOI https://doi.org/10.1111/mmi.14338  PMID: 31254421

    Q & A Petra Anne Levin (2019) Curr Biol 29: R395–R402

    Si, F, G. Le Treut, J. T. Sauls, S. Vadia, P. A. Levin, and S.  Jun (2019) Mechanistic origin of cell-size control and homeostasis in bacteria, Curr Biol 29:760-1770.e7. doi: 10.1016/j.cub.2019.04.062  PMID: 31104932  Preprint: https://www.biorxiv.org/content/early/2018/11/26/478818

    Taheri-Araghi, S and P. A. Levin (2019) One is nothing without the other: theoretical and empirical analysis of cell growth and cell cycle progression,J Mol Biol 431:2061-2067. doi: 10.1016/j.jmb.2019.04.004 PMID: 31026450

    Mueller, E. A., A. J. F. Egan, E. Breukink, W. Vollmer, and P. A. Levin (2019) Plasticity in Escherichia coli cell wall metabolism promotes fitness and antibiotic resistance across environmental conditions, eLife, 2019;8:e40754 DOI: 10.7554/eLife.40754 PMID: 30963998 

    Mueller, E. A. and C. S. Westfall (2019) Blown out of proportion — The role of ppGpp in balanced metabolism. Small Things Considered Blog, March 11, 2019. Link here.

    McAuley, S., S. Vadia, C. Jani, A. Huynh, Z. Yang, P. A. Levin, and J. Nodwell (2019) A chemical inhibitor of cell growth reduces cell size in Bacillus subtilis, ACS Chem. Biol. 14(4) 688-695. PMID: 30848888

    Westfall, C. S., A. L. Flores-Mireles, J. I. Robinson, A. J. L. Lynch, S. Hultgren, J. P. Henderson, and P. A. Levin (2019) The widely used antimicrobial triclosan induces high levels of antibiotic tolerance in vitro and reduces antibiotic efficacy up to 100-fold in vivo. Antimicrob Agents Chemother. doi: 10.1128/AAC.02312-18. PMID:30782996

    Hill, N. S., J. Zuke, P. J. Buske, and P. A. Levin (2018) A nutrient-dependent division antagonist is regulated post-translationally by the Clp proteases in Bacillus subtilisBMC Microbiology, In press

    Wehrens, M., D. Ershov, R. Rozendaal, N. Walker, D. Schultz, R. Kishony, P. A. Levin, and S. J. Tans (2018) Size Laws and Division Ring Dynamics in Filamentous Escherichia coli cells, Curr Biol 28: 1-8.  doi.org/10.1016/j.cub.2018.02.006

    Westfall, C. S. and P. A. Levin (2018) Comprehensive analysis of central carbon metabolism reveals multiple connections between nutrients, biosynthetic capacity, and cell morphology in Escherichia coli, PLOS Genetics, 14(2) e1007205doi.org/10.1371/journal.pgen.1007205

    Westfall, C.S. and P. A. Levin (2017) Bacterial Cell Size: Multifactorial and Multifaceted, Invited review for Annual Review of Microbiology, 71: 499-517. PMID: 28886685     DOI: 10.1146/annurev-micro-090816-093803

    Vadia, S., J. L. Tse, R. Lucena, D. Kellogg, J. Wang, and P. A. Levin (2017) Fatty acid synthesis sets cell envelope capacity and dictates microbial cell size, Current Biology 27 (12):1757 - 1767.e5 PMID: 28602657 DOI: http://dx.doi.org/10.1016/j.cub.2017.05.076

    Vadia, S. and P. A. Levin (2017) Bacterial Size: Can’t escape the long arm of the law. Curr Biol 27:R339-R341. PMID:28486115  DOI: 10.1016/j.cub.2017.03.050.

    den Blaauwen, T., L. W. Hamoen, and P. A. Levin (2017) The Divisome at 25: The road ahead, Curr Opin Microbiol36:85–94  PMID: 28254403  DOI:10.1016/j.mib.2017.01.001 

    Arjes, H.A., B. Lai, E. R. Emelue, A. Steinbach, and P. A. Levin (2015) Mutations in the bacterial cell division protein FtsZ highlight the role of GTP binding and longitudinal subunit interactions in assembly and function. BMC Microbiology, 5:209 DOI 10.1186/s12866-015-0544-z.

    Levin, P. A. and E. R. Angert, Small but mighty: cell size and bacteria (2015) invited chapter for Cold Spring Harbor Perspectives: Size Control in Biology, from Organelles to Organisms. Edited by Drs. Rebecca Heald, Iswar Hariharan, and David Wake, 7(7):a019216. doi: 10.1101/cshperspect.a019216. PMID:26054743

    Land, A.D., P. Hogan, S. Fritz and P. A. Levin, (2015) Phenotypic variation is almost entirely independent of the host-pathogen relationship in clinical isolates of S. aureus, PLoS ONE, 10(6):e0129670. doi: 10.1371/journal.pone.0129670. PMID: 26098551