The primary aim of this research is to further characterise the role of autophagy and other host immune pathways in the regulation of Wolbachia populations in mosquito and nematode hosts. This in turn will enhance our understanding of the therapeutic mode-of-action of anti-Wolbachia drugs to improve future drug design in treatment of filarial diseases. Initial experimental approaches were done to examine autophagy contribution in anti-Wolbachia activity of drugs by inhibiting autophagy using chemical manipulations. Autophagy inhibition was assessed on the molecular and cellular biology of host cells and nematodes, at the cellular level using Wolbachia-infected cell lines and on the organism level using filarial nematode Brugia malayi. This was achieved with the use of high throughput imaging system (Operetta) and quantitative polymerase chain reaction (qPCR). Following antibiotic treatment with doxycycline and rifampicin both at a concentration of 5µM, bacteria load was significantly reduced compared to untreated control groups. Whereas, the addition of an autophagy inhibitor (wortmannin) reduced antibiotic activity to eliminate Wolbachia. These initial results further consolidate our theory that autophagy is essential for eliminating Wolbachia within hosts when administering anti-Wolbachia drugs. Further experimentation will be to test whether activation of autophagy (using autophagy chemical promotors) can reduce bacteria load in a similar manner to antibacterial drugs and act as a target to improve the potency of existing anti-Wolbachia drugs and shorten current treatment regimens.
