Benjamin Paul Bratton, Ph.D.

Assistant Professor

benjamin.p.bratton.1@vanderbilt.edu
Faculty Appointments
Assistant Professor of Pathology, Microbiology and Immunology Assistant Professor of Cell & Developmental Biology
Education
Ph.D., Chemistry, University of Wisconsin, Madison, Wisconsin
Office Address
Medical Center North, CC2201A
Research Description
Bacterial cells exhibit incredible subcellular organization even though they are only about one micron, roughly one million times smaller than humans. This organization is crucial to the health and development of the organism. The characteristic rod, helical, and curved morphologies of bacteria are patterned by one of the key organized components, the bacterial cytoskeleton. The cytoskeleton patterns the growth and recycling of the rigid cell wall, breaking symmetry and establishing specific cell shapes. These physical shapes are key factors in how bacteria interact with their physical environments, including the ability of pathogens to invade and colonize host sites. To study these subcellular processes, our lab develops new light microscopy and computational image reconstruction technologies to understand both general principles and species specific nuances to bacterial shape maintenance.

The scientific approaches used by our lab borrow heavily from the domains of microbial genetics, light microscopy, optogenetics, biophysics, computational image processing, and machine learning. While some specific projects are focused in one area, an interdisciplinary approach is crucial to understand, manipulate, and utilize the biophysical principles underlying bacterial cell biology. Targeting the bacterial cell wall has been one of the greatest successes of antibiotics, and I am therefore interested in the molecular factors that govern cell wall biosynthesis and cell shape. Three major focuses of my lab are understanding the biophysical mechanisms modulating cell shape, advancing multidimensional reconstructions of bacterial cell shape, and developing subcellular optogenetic tools to control bacterial growth.

MreB is a widely conserved bacterial actin that plays key roles in cell shape determination and is geometrically localized, making it an ideal candidate protein to study the molecular mechanism of geometric localization. My lab utilizes both chemical and genetic perturbations to probe how the features of MreB assembly, localization, and dynamics are associated with the multifaceted aspects of cell shape. These data driven investigations require both the full three-dimensional reconstructions of bacterial cells and machine learning technologies. In particular, my lab continues to develop and advance fluorescence microscopy technologies which allow us to reconstruct the shape of individual cells. As the shape of bacterial cells is modified by the growth of and recycling of cell wall, we are developing novel methods to incorporate temporal dynamics into our shape reconstructions. These technologies are useful not only for studying the simple cylindrical rod morphology of Escherichia coli, but also more complex geometries such as the curved rod Vibrio cholerae and the helical rod Helicobacter pylori. In addition to developing and applying new computational techniques for shape reconstruction, our lab is also developing new microscopy techniques to geometrically position specific protein activity. These optogenetic approaches will allow us to close the loop of understanding and test predictions generated from our observations of the importance of spatiotemporal organization in bacterial cell biology.

See more at www.vumc.org/bratton-lab
Research Keywords
bacterial cell biology, biophysics, light microscopy, computational microbiology, Escherichia coli, Caulobacter crescentus, Vibrio cholerae, Helicobacter pylori
Publications
Islam ST, Jolivet NY, Cuzin C, Belgrave AM, My L, Fleuchot B, Faure LM, Mahanta U, Kezzo AA, Saïdi F, Sharma G, Fiche JB, Bratton BP, Herrou J, Nollmann M, Shaevitz JW, Durand E, Mignot T. Unmasking of the von Willebrand A-domain surface adhesin CglB at bacterial focal adhesions mediates myxobacterial gliding motility. Sci Adv [print-electronic]. 2023 Feb 2/22/2023; 9(8): eabq0619. PMID: 36812310, PMCID: PMC9946355, DOI: 10.1126/sciadv.abq0619, ISSN: 2375-2548.

Sichel SR, Bratton BP, Salama NR. Distinct regions of H. pylori's bactofilin CcmA regulate protein-protein interactions to control helical cell shape. Elife. 2022 Sep 9/8/2022; 11: PMID: 36073778, PMCID: PMC9507126, PII: 80111, DOI: 10.7554/eLife.80111, ISSN: 2050-084X.

Scheffler RJ, Bratton BP, Gitai Z. Pseudomonas aeruginosa clinical blood isolates display significant phenotypic variability. PLoS One. 2022; 17(7): e0270576. PMID: 35793311, PMCID: PMC9258867, PII: PONE-D-22-01014, DOI: 10.1371/journal.pone.0270576, ISSN: 1932-6203.

Martin NR, Blackman E, Bratton BP, Chase KJ, Bartlett TM, Gitai Z. CrvA and CrvB form a curvature-inducing module sufficient to induce cell-shape complexity in Gram-negative bacteria. Nat Microbiol [print-electronic]. 2021 Jul; 6(7): 910-20. PMID: 34183815, PII: 10.1038/s41564-021-00924-w, DOI: 10.1038/s41564-021-00924-w, ISSN: 2058-5276.

Scheffler RJ, Sugimoto Y, Bratton BP, Ellison CK, Koch MD, Donia MS, Gitai Z. Pseudomonas aeruginosa detachment from surfaces via a self-made small molecule. J Biol Chem [print-electronic]. 2021 Jan; 296: 100279. PMID: 33450229, PMCID: PMC7949062, PII: S0021-9258(21)00047-8, DOI: 10.1016/j.jbc.2021.100279, ISSN: 1083-351X.

Martin JK, Sheehan JP, Bratton BP, Moore GM, Mateus A, Li SH, Kim H, Rabinowitz JD, Typas A, Savitski MM, Wilson MZ, Gitai Z. A Dual-Mechanism Antibiotic Kills Gram-Negative Bacteria and Avoids Drug Resistance. Cell [print-electronic]. 2020 Jun 6/25/2020; 181(7): 1518-1532.e14. PMID: 32497502, PMCID: PMC7780349, PII: S0092-8674(20)30567-5, DOI: 10.1016/j.cell.2020.05.005, ISSN: 1097-4172.

Taylor JA, Bratton BP, Sichel SR, Blair KM, Jacobs HM, DeMeester KE, Kuru E, Gray J, Biboy J, VanNieuwenhze MS, Vollmer W, Grimes CL, Shaevitz JW, Salama NR. Distinct cytoskeletal proteins define zones of enhanced cell wall synthesis in Helicobacter pylori. Elife. 2020 Jan 1/9/2020; 9: PMID: 31916938, PMCID: PMC7012605, PII: 52482, DOI: 10.7554/eLife.52482, ISSN: 2050-084X.

Bratton BP, Barton B, Morgenstein RM. Three-dimensional Imaging of Bacterial Cells for Accurate Cellular Representations and Precise Protein Localization. J Vis Exp. 2019 Oct 10/29/2019; (152): PMID: 31736495, DOI: 10.3791/60350, ISSN: 1940-087X.

Sanfilippo JE, Lorestani A, Koch MD, Bratton BP, Siryaporn A, Stone HA, Gitai Z. Microfluidic-based transcriptomics reveal force-independent bacterial rheosensing. Nat Microbiol [print-electronic]. 2019 Aug; 4(8): 1274-81. PMID: 31086313, PMCID: PMC6656604, PII: 10.1038/s41564-019-0455-0, DOI: 10.1038/s41564-019-0455-0, ISSN: 2058-5276.

Guzzo M, Murray SM, Martineau E, Lhospice S, Baronian G, My L, Zhang Y, Espinosa L, Vincentelli R, Bratton BP, Shaevitz JW, Molle V, Howard M, Mignot T. A gated relaxation oscillator mediated by FrzX controls morphogenetic movements in Myxococcus xanthus. Nat Microbiol [print-electronic]. 2018 Aug; 3(8): 948-59. PMID: 30013238, PII: 10.1038/s41564-018-0203-x, DOI: 10.1038/s41564-018-0203-x, ISSN: 2058-5276.

Bratton BP, Shaevitz JW, Gitai Z, Morgenstein RM. MreB polymers and curvature localization are enhanced by RodZ and predict E. coli's cylindrical uniformity. Nat Commun. 2018 Jul 7/18/2018; 9(1): 2797. PMID: 30022070, PMCID: PMC6052060, PII: 10.1038/s41467-018-05186-5, DOI: 10.1038/s41467-018-05186-5, ISSN: 2041-1723.

Shi H, Bratton BP, Gitai Z, Huang KC. How to Build a Bacterial Cell: MreB as the Foreman of E. coli Construction. Cell. 2018 Mar 3/8/2018; 172(6): 1294-305. PMID: 29522748, PMCID: PMC5846203, PII: S0092-8674(18)30227-7, DOI: 10.1016/j.cell.2018.02.050, ISSN: 1097-4172.

Bartlett TM, Bratton BP, Duvshani A, Miguel A, Sheng Y, Martin NR, Nguyen JP, Persat A, Desmarais SM, VanNieuwenhze MS, Huang KC, Zhu J, Shaevitz JW, Gitai Z. A Periplasmic Polymer Curves Vibrio cholerae and Promotes Pathogenesis. Cell [print-electronic]. 2017 Jan 1/12/2017; 168(1-2): 172-185.e15. PMID: 28086090, PMCID: PMC5287421, PII: S0092-8674(16)31735-4, DOI: 10.1016/j.cell.2016.12.019, ISSN: 1097-4172.

Liu GS, Bratton BP, Gitai Z, Shaevitz JW. The effect of antibiotics on protein diffusion in the Escherichia coli cytoplasmic membrane. PLoS One. 2017; 12(10): e0185810. PMID: 28977034, PMCID: PMC5627921, PII: PONE-D-17-28517, DOI: 10.1371/journal.pone.0185810, ISSN: 1932-6203.

Gaal T, Bratton BP, Sanchez-Vazquez P, Sliwicki A, Sliwicki K, Vegel A, Pannu R, Gourse RL. Colocalization of distant chromosomal loci in space in E. coli: a bacterial nucleolus. Genes Dev. 2016 Oct 10/15/2016; 30(20): 2272-85. PMID: 27898392, PMCID: PMC5110994, PII: 30/20/2272, DOI: 10.1101/gad.290312.116, ISSN: 1549-5477.

Ouzounov N, Nguyen JP, Bratton BP, Jacobowitz D, Gitai Z, Shaevitz JW. MreB Orientation Correlates with Cell Diameter in Escherichia coli. Biophys J. 2016 Sep 9/6/2016; 111(5): 1035-43. PMID: 27602731, PMCID: PMC5018124, PII: S0006-3495(16)30580-X, DOI: 10.1016/j.bpj.2016.07.017, ISSN: 1542-0086.

Nguyen JP, Bratton BP, Shaevitz JW. Biophysical Measurements of Bacterial Cell Shape. Methods Mol Biol. 2016; 1440: 227-45. PMID: 27311676, DOI: 10.1007/978-1-4939-3676-2_17, ISSN: 1940-6029.

Morgenstein RM, Bratton BP, Nguyen JP, Ouzounov N, Shaevitz JW, Gitai Z. RodZ links MreB to cell wall synthesis to mediate MreB rotation and robust morphogenesis. Proc Natl Acad Sci U S A [print-electronic]. 2015 Oct 10/6/2015; 112(40): 12510-5. PMID: 26396257, PMCID: PMC4603514, PII: 1509610112, DOI: 10.1073/pnas.1509610112, ISSN: 1091-6490.

Bratton BP, Shaevitz JW. Simple Experimental Methods for Determining the Apparent Focal Shift in a Microscope System. PLoS One. 2015; 10(8): e0134616. PMID: 26270960, PMCID: PMC4536040, PII: PONE-D-15-08861, DOI: 10.1371/journal.pone.0134616, ISSN: 1932-6203.

Bakshi S, Choi H, Rangarajan N, Barns KJ, Bratton BP, Weisshaar JC. Nonperturbative imaging of nucleoid morphology in live bacterial cells during an antimicrobial peptide attack. Appl Environ Microbiol [print-electronic]. 2014 Aug; 80(16): 4977-86. PMID: 24907320, PMCID: PMC4135745, PII: AEM.00989-14, DOI: 10.1128/AEM.00989-14, ISSN: 1098-5336.

Bakshi S, Bratton BP, Weisshaar JC. Subdiffraction-limit study of Kaede diffusion and spatial distribution in live Escherichia coli. Biophys J [print-electronic]. 2011 Nov 11/16/2011; 101(10): 2535-44. PMID: 22098753, PMCID: PMC3218334, PII: S0006-3495(11)01202-1, DOI: 10.1016/j.bpj.2011.10.013, ISSN: 1542-0086.

Bratton BP, Mooney RA, Weisshaar JC. Spatial distribution and diffusive motion of RNA polymerase in live Escherichia coli. J Bacteriol [print-electronic]. 2011 Oct; 193(19): 5138-46. PMID: 21784927, PMCID: PMC3187386, PII: JB.00198-11, DOI: 10.1128/JB.00198-11, ISSN: 1098-5530.

Mondal J, Bratton BP, Li Y, Yethiraj A, Weisshaar JC. Entropy-based mechanism of ribosome-nucleoid segregation in E. coli cells. Biophys J. 2011 Jun 6/8/2011; 100(11): 2605-13. PMID: 21641305, PMCID: PMC3117155, PII: S0006-3495(11)00475-9, DOI: 10.1016/j.bpj.2011.04.030, ISSN: 1542-0086.

Konopka MC, Sochacki KA, Bratton BP, Shkel IA, Record MT, Weisshaar JC. Cytoplasmic protein mobility in osmotically stressed Escherichia coli. J Bacteriol [print-electronic]. 2009 Jan; 191(1): 231-7. PMID: 18952804, PMCID: PMC2612437, PII: JB.00536-08, DOI: 10.1128/JB.00536-08, ISSN: 1098-5530.