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http://hdl.handle.net/11375/21112
Title: | cAMP-independent and dependent regulation of Pseudomonas aeruginosa twitching motility |
Authors: | Buensuceso, Ryan Nicholas Carlos |
Advisor: | Burrows, Lori L. |
Department: | Biochemistry and Biomedical Sciences |
Keywords: | Pseudomonas aeruginosa;Type IV Pilus;Twitching motility |
Publication Date: | 2017 |
Abstract: | Type IVa pili (T4aP) are long, retractile, filamentous, surface appendages involved in cellular surface adhesion, biofilm formation, DNA uptake, and a unique form of motility called ‘twitching’. They are a critical virulence factor in a number of bacteria, including the opportunistic pathogen Pseudomonas aeruginosa, a major cause of hospital-acquired infections. T4aP function is controlled by a number of different regulatory proteins and systems. A putative chemosensory system termed ‘Chp’, controls levels of the second messenger molecule cyclic adenosine monophosphate (cAMP). cAMP works with a cAMP receptor protein called Vfr to control expression of ~200 virulence genes, including those that are required to make T4aP. cAMP levels are regulated by proteins outside the Chp system, including the bitopic inner membrane protein, FimV. This study examines the role of the Chp system and FimV in T4aP regulation. Both proteins are required for regulation of cAMP levels, while the Chp system also has a cAMP-independent role in regulating twitching. FimV has been shown to regulate cAMP levels, possibly connecting to the Chp system through a scaffold protein, FimL. We present the structure of a conserved cytoplasmic region of FimV, and show that this region is required for connecting FimV to the Chp system. We also characterize the cAMP-independent role of FimV, confirming that it is distinct from that of the Chp system, and is involved in localizing T4P regulatory proteins. We also provide evidence that the cAMP-independent role of the Chp system is to mediate the balance between T4P extension and retraction, possibly through denoting the ‘front’ of a motile cell. Together, these data help to resolve the cAMP-independent and –dependent pathways controlling twitching motility. |
URI: | http://hdl.handle.net/11375/21112 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Buensuceso_Ryan_NC_201612_PhD.pdf | 42.98 MB | Adobe PDF | View/Open |
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