Flagellar assembly is complex and coupled to the controlled expression of more than 70 genes in the flagellar and chemotaxis regulon. It takes many cell generations to assemble a completed flagellum. For 25 years my lab has investigated mechanisms that couple flagellar gene expression to assembly. In addition, about 20 regulators have been identified that couple induction or inhibition of flagellar synthesis to different environmental conditions that are sensed by numerous global regulatory pathways in the cell. The focus of this grant application is to determine mechanisms involved in localized transcription and translation mechanisms of flagellar genes at the base of the flagellar structures in the cytoplasm. The research will also determine how a few specific proteins are selected from the thousands present in the cytoplasm and targeted for secretion. How does the coordinate the assembly of multiple structures within the same cell? Our preliminary data suggests that coordinating the assembly of multiple structures within an individual cell occurs by compartmentalization in 3-dimensional space to generate independent construction sites in the cell.
Salmonella enterica causes significant disease in humans and animals. Like many gram- negative pathogens utilizes its flagellar organelles for motility and pathogenesis. Both motility- and virulence-associated type III secretion systems play important roles in the infection process and their characterization provides numerous potential drug targets for development of therapeutic agents.
| Wozniak, Christopher E; Lin, Zhenjian; Schmidt, Eric W et al. (2018) Thailandamide, a Fatty Acid Synthesis Antibiotic That Is Coexpressed with a Resistant Target Gene. Antimicrob Agents Chemother 62: |
| Cohen, Eli J; Ferreira, Josie L; Ladinsky, Mark S et al. (2017) Nanoscale-length control of the flagellar driveshaft requires hitting the tethered outer membrane. Science 356:197-200 |
| Paradis, Guillaume; Chevance, Fabienne F V; Liou, Willisa et al. (2017) Variability in bacterial flagella re-growth patterns after breakage. Sci Rep 7:1282 |
| Tu, Jiagang; Park, Taehyun; Morado, Dustin R et al. (2017) Dual host specificity of phage SP6 is facilitated by tailspike rotation. Virology 507:206-215 |
| Erhardt, Marc; Wheatley, Paige; Kim, Eun A et al. (2017) Mechanism of type-III protein secretion: Regulation of FlhA conformation by a functionally critical charged-residue cluster. Mol Microbiol 104:234-249 |
| Chevance, Fabienne F V; Hughes, Kelly T (2017) Case for the genetic code as a triplet of triplets. Proc Natl Acad Sci U S A 114:4745-4750 |
| Hughes, Kelly T (2016) Mg2+-dependent translational speed bump acts to regulate gene transcription. Proc Natl Acad Sci U S A 113:14881-14883 |
| Wee, Daniel H; Hughes, Kelly T (2015) Molecular ruler determines needle length for the Salmonella Spi-1 injectisome. Proc Natl Acad Sci U S A 112:4098-103 |
| Hendrix, Roger W; Ko, Ching-Chung; Jacobs-Sera, Deborah et al. (2015) Genome Sequence of Salmonella Phage ?. Genome Announc 3: |
| Chevance, Fabienne F V; Le Guyon, Soazig; Hughes, Kelly T (2014) The effects of codon context on in vivo translation speed. PLoS Genet 10:e1004392 |
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