Doctor of Philosophy (PhD)
The global incidence of arthropod-borne diseases such as dengue fever and spotted fever rickettsiosis has dramatically increased over the past decades. Prevention and control of arthropod-borne diseases depends on effective measures to control vector populations. Yet, development of pesticide resistance has reduced the efficacy of vector control programs, which highlights the need for novel strategies to prevent arthropod-borne diseases. For arthropod-borne pathogens, once in the vector hemocoel, they must evade the host immune system and salivary gland barrier to enable horizontal transmissions. Therefore, understanding pathogen-vector interactions in the hemocoel and vector salivary gland function would benefit arthropod-borne diseases control programs. In mosquitoes and ticks, the role of potassium channels in regulating pathogen progression in the hemocoel is poorly defined. My dissertation projects aimed to characterize the physiological roles of potassium channels in mosquito and tick salivary gland secretion, mosquito dorsal vessel function and antiviral immune responses, which may fill the knowledge gap towards the development of novel intervention strategies to prevent vector-borne diseases. Four objectives were included in my dissertation: 1) Define the roles of KATP channels in mosquito salivation, feeding, and vector competency; 2) Define KATP channel regulation of circulatory homeostasis and antiviral immune responses to dengue virus infection; 3) Test the effect of KATP channel modulation to the secreted proteome and temporal distribution of KATP channel proteins during tick feeding; 4) Test changes to tick salivary gland membrane physiology after Rickettsia infection. Our data demonstrated that KATP channels are critical for mosquito blood feeding and dengue virus (DENV) competence. We also found mosquito hemocytes are likely to be antiviral, and KATP channel agonist pinacidil can reduce DENV viral load from mosquitoes, which effect might be linked with mosquito circulatory system, as KATP channel modulators can regulate mosquito’s dorsal vessel contraction rate. In ticks, KATP channel proteins were dynamically expressed in the salivary gland during feeding. Modulators of KATP channels were found to regulate the saliva protein secretion represented by the anticoagulant saliva protein AV422 during tick early feeding phase. Rickettsial invasion was found to depolarize host cell membrane potential. Manipulation on cell membrane potential would affect rickettsial salivary gland invasion. In summary, data generated by this dissertation enables more understanding on pathogen-vector interactions and might help to identify targets for novel chemistry or vaccines in disease control programs.
Li, Zhilin, "Defining Pathogen-Vector Interactions in Arthropod Salivary Glands and the Utility of Potassium Ion Channels to Inhibit Vector Competency" (2022). LSU Doctoral Dissertations. 6002.
Swale, Daniel R.
Available for download on Wednesday, October 31, 2029