Description |
The flagellum allows both Gram-negative and Gram-positive bacteria to swim towards favorable environments and colonize new sites. However, the injectisome is unique to Gram-negative pathogenic bacteria. Injectisomes are utilized to secrete effector proteins into host cells where they influence the cell's behavior and evade the immune response. The flagellar hook and injectisome needle have evolved to optimal lengths to facilitate motility and pathogenicity, respectively. The mechanism of length control also plays a central role in their assembly process. Many factors can alter the lengths of these structures, which has influenced researchers in the field to propose different length-control models. The works presented in this dissertation provide a detailed description of the experiments and logic that have led to elucidating one model of length control based on a secreted molecular ruler in both flagellar and injectisome systems. Chapter 1 provides a review of the structural architecture, assembly process and genetic regulation of the flagella and injectisome of Salmonella enterica serovar Typhimurium. This chapter also provides a brief overview and history of the different length control models that have been proposed for the hook- and needle-length control. Chapters 2 and 3 focuses on the flagellar length-control mechanism. Here, a model of length control, called the cup model, was questioned and was experimentally found to be a misinterpretation of previous data (Chapter 2). This work also provided key insights into the mechanism of how hook length is determined by the molecular ruler, FliK (Chapter 3). Chapter 4 of this work supports the assertion that the molecular ruler mechanism for length control is conserved throughout type-III secretion systems. We refuted the data published in support of an inner-rod model of length control in the Spi-1 injectisome. The findings presented in this thesis are concluded in Chapter 5, as well as further insights into the length-control and assembly mechanisms of type-III secretion systems uncovered during our investigations to provide a complete model for length control and uncover the conservation of a molecular ruler length determinant in type-III secretion systems. |