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Kelly Hughes

Professor of Biological Sciences

Biological Process in Bacteria

Kelly Hughes Photo

 

Molecular Biology Program

Education

B.S. University of California, Irvine

Ph.D. University of Utah

 

Research

Bacteria swim up chemical gradients, propelled by some of the tiniest, complex motors in the biosphere. The bacterial flagellum is one of the most remarkable structures in nature: a complex self-assembling nanomachine that allows bacteria to move in their environment. Assembly of large and complex organelles, such as the bacterial flagellum, poses the formidable problem of building substructures to specific design requirements that maximize efficiency. This process utilizes structural scaffolds, molecular rulers & clocks, a corking device, a cell wall penetration mechanism, the energy of the proton motive force, and secretion pilots, to facilitate the assembly process. In addition to mechanism that control assembly of specific substructures, the bacterium has mechanisms that couple temporal gene expression to specific stages of the organelle assembly process. In this way, structures required late in the assembly process are not synthesized until the precursor structures have been completed and genes for structures already completed are turned off.

References

  1. Johnson S, Furlong EJ, Deme JC, Nord AL, Caesar J, Chevance FFV, Berry RM, Hughes KT, Lea SM. Molecular structure of the intact bacterial flagellar basal body. Nature Microbiol. (2021), 6: 712-721.
  2. Plitnick J, Chevance FFV, Stringer A, Hughes KT, Wade JT. Regulatory crosstalk between motility and interbacterial communication in SalmonellaTyphimurium. J. Bacteriol. (2021), 203: e00510-520.
  3. Akhade AS, Atif SM, Lakshmi BS, Dikshit N, Hughes KT, Qadri A, Subramanian N. Type 1 interferon-dependent repression of NLRC4 and iPLA2 licenses downregulation of Salmonella flagellin inside macrophages. (2020), Proc. Nat. Acad. Sci. USA, 117: 29811-29822.
  4. Wozniak CE, Hendriksen JJ, Olivera BM, Roth JR, Hughes KT. Integration of the pSLT plasmid into the Salmonella chromosome results in a temperature-sensitive growth defect due to aberrant DNA replication. J. Bacteriol. (2020), 202: e00380-20.
  5. Horstmann J, Lunelli M, Cazzola H, Heidemann J, Kühne C, Steffen P, Szefs S, Rossi C, Lokareddy R, Wang C, Lemaire L, Hughes KT, Uetrecht C, Schlüter H, Grassl G, Stradal T, Rossez Y, Kolbe M, Erhardt M. Methylation of Salmonella Typhimurium flagella promotes bacterial adhesion and host cell invasion. Nat. Commun. (2020), 11: 2013.
  6. Wozniak CE, Lin Z, Schmidt EW, Hughes KT, Liou TG. Thailandamide, a fatty acid synthesis antibiotic that is coexpressed with a resistant target gene. Antimicrob. Agents Chemother. (2018), 62: e00463-18.
  7. Ward E, Renault TT, Erhardt M, Hughes KT, Blair DF. Type-III Secretion Pore Formed by Flagellar Protein FliP. Molec. Microbiol. (2018), 107: 94-103.
  8. Asmar A, Ferreira JL, Cohen EJ, Cho SH, Beeby M, Hughes KT, Collet JF. Communication across the bacterial cell envelope depends on the size of the periplasm. PLOS Biology (2017), 15: e2004303.
  9. Paradis G, Chevance FFV, Liou W, Renault TT, Hughes KT, Rainville S, Erhardt M. Variability in bacterial flagella re-growth patterns after breakage. Sci Rep. (2017) 7:1282 (1-10).
  10. Tu J, Park T, Morado DR, Hughes KT, Molineux IJ, Liu J. Dual host specificity of phage SP6 is facilitated by tailspike rotation. Virology (2017) 507: 206-215.
  11. Cohen EJ, Ferreira J, Ladinsky MS, Beeby M, Hughes KT. Nano-scale length control of the flagellar drive-shaft requires hitting the protein-tethered outer membrane. Science (2017), 356: 197-200.
  12. Chevance FFV, Hughes KT. Case for the genetic code as a triplet-of-triplets. Proc. Natl. Acad. Sci. USA. (2017), 114: 4745-4750.
  13. Fujii T, Kato T, Hiraoka KD, Miyata T, Minamino T, Chevance FF, Hughes KT, Namba K. Identical folds used for distinct mechanical functions of the bacterial flagellar rod and hook. Nat. Commun. (2017) 8:14276 (1-10).
  14. Erhardt M, Wheatley P, Kim EA, Hirano T, Zhang Y, Sarkar MK, Hughes KT, Blair DF. Mechanism of type-III protein secretion: Regulation of FlhA conformation by a functionally critical charged-residue cluster. Mol. Microbiol. (2017), 104: 234-249.
  15. Hughes KT. Mg2+-dependent translational speed bump acts to regulate gene transcription. Proc. Natl. Acad. Sci. USA. (2016), 113: 14881-14883
  16. Hengge R, Galperin MY, Ghigo JM, Gomelsky M, Green J, Hughes KT, Jenal U, and Landini P. Systematic Nomenclature for GGDEF and EAL Domain-Containing Cyclic Di-GMP Turnover Proteins of Escherichia coli. J Bacteriol. (2015), 198: 7-11.
  17. Wee DH, and Hughes KT. Molecular ruler determines needle length for the Salmonella Spi-1 injectisome. Proc Natl Acad Sci U S A. (2015), 112: 4098-103.
  18. Hendrix RW, Ko CC, Jacobs-Sera D, Hatfull GF, Erhardt M, Hughes KT, and Casjens SR. Genome Sequence of Salmonella Phage χ. Genome Announc. (2015), 3 pii:e01229-1.
  19. Sato Y, Takaya A, Mouslim C, Hughes KT, and Yamamoto T. FliT selectively enhances proteolysis of FlhC subunit in FlhD4C2 complex by an ATP-dependent protease, ClpXP. J Biol Chem. (2014), 289: 33001-11.
  20. Erhardt M, Mertens ME, Fabiani FD, and Hughes KT. ATPase-independent type-III protein secretion in Salmonella enterica. PLoS Genet. (2014), 10: e1004800.
  21. Singer, H.M., M. Erhardt, and K.T. Hughes. Comparative analysis of the secretion capability of early and late flagellar type III secretion substrates. Molec. Microbiol. (2014), 93: 505-20.
  22. Cohen, E.J., and K.T. Hughes. Rod to hook transition for extracellular flagellum assembly is catalyzed by the L-ring-dependent rod-scaffold removal. J. Bacteriol. (2014), 196: 2387-2395.
  23. Guo, S., I. Alshamy, K.T. Hughes, and F.F.V. Chevance. Analysis of factors that affect FlgM-dependent type III secretion for protein purification with Salmonella Typhimurium. J. Bacteriol. (2014), 196: 2333-2347.
  24. Chevance, F.F.V., S. Le Guyon, and K.T. Hughes. The effects of codon context on in vivo translation speed. PLoS Genetics (2014), 10: e1004392.
  25. Mouslim, C., and K.T. Hughes. The effect of cell growth phase on the regulatory cross-talk between flagellar and Spi1 virulence gene expression. PLoS Pathog. (2014), 10: e1003987.
  26. Singer, H.M., C. Kühne, J.A. Deditius, K.T. Hughes, and M. Erhardt. The Salmonella Spi1 virulence regulatory protein protein HilD directly activates transcription of the flagellar master operon flhDC. J. Bacteriol. (2014), 196: 1448-1457.
  27. Galeva, A., N. Moroz, Y.H. Yoon, K.T. Hughes, F.A. Samatey, and A.S. Kostyukova. Bacterial flagellin-specific chaperone FliS interacts with anti-sigma factor FlgM. J. Bacteriol. (2014), 196: 1215-1221.
  28. Kawamoto, A., Y.V. Morimoto, T. Miyata, T. Minamino, K.T. Hughes, T. Kato, and K. Namba. Common and distinct structural features of Salmonella injectisome and flagellar basal body. Sci Rep. (2013), 3: 3369.
  29. Singer, H.M., M. Erhardt, and K.T. Hughes. RflM functions as a transcriptional repressor in the autogenous control of the Salmonella flagellar master operon flhDC. J. Bacteriol. (2013), 195: 4274-4282.
  30. Singer, H.M., M. Erhardt, A.M. Steiner, M.M. Zhang, D. Yoshikami, G. Bulaj, B.M. Olivera, and K.T. Hughes. Selective purification of recombinant neuroactive peptides using the flagellar type III secretion system. MBio (2012), 3: 1-9.
  31. Takaya, A., M. Erhardt, K. Karata, K. Winterberg, T. Yamamoto, and K.T. Hughes. YdiV: a dual function protein that targets FlhDC for ClpXP-dependent degradation by promoting release of DNA-bound FlhDC complex. Molec. Microbiol. (2012), 83: 1268-1284.
  32. Briegel, A., X. Li, A.M. Bilwes, K.T. Hughes, G.J. Jensen, and B.R. Crane. Bacterial chemoreceptor arrays are hexagionally packed trimmers of receptor dimers networked by rings of kinase and coupling proteins. Proc. Natl. Acad. Sci. USA (2012), 109: 3766-3771.
  33. Erhardt, M., and K.T. Hughes. C-ring requirement in flagellar type III secretion is bypassed by FlhDC upregulation. Molec. Microbiol. (2010), 75: 376-393.
  34. Erhardt, M., T. Hirano, Y. Su, K. Paul, R., Wee, D.H., Mizuno, S.-I. Aizawa, and K.T. Hughes. The role of the FliK molecular ruler in hook-length control in Salmonella enterica. Molec. Microbiol. (2010), 75: 1272-1284.
  35. Wozniak, C.E., F.F.V. Chevance, and Hughes KT. Multiple promoters contribute to swarming and the coordination of transcription with flagellar assembly in Salmonella. J. Bacteriol. (2010), 192: 4752-4762.
  36. Erhardt, M., H.M. Singer, D.H. Wee, J.P. Keener, and K.T. Hughes. An infrequent molecular ruler controls flagellar hook length in Salmonella enterica. EMBO J. (2011), 30: 2948-61.
Last Updated: 7/17/21