AbstractsBiology & Animal Science

Burkholderia pseudomallei, a gram-negative bacterium, is the causative agent of melioidosis, which is endemic in tropical areas such as South East Asia and Northern Australia and results in significant mortality. B. pseudomallei is able to invade both non-phagocytic cells and phagocytic cells, escape from the endosome/phagosome and replicate within the cytosol (Wiersinga et al., 2012). Once in the cytosol, B. pseudomallei expresses the protein, BimA, that affords the bacteria actin-based motility allowing them to spread to neighbouring cells, resulting in cell fusion and then ultimately the formation of multinucleated giant cells (MNGCs) (Stevens et al., 2005a, Kespichayawattana et al., 2000). The signalling pathways and mechanisms active during bacterial invasion and the host response have yet to be fully determined. Autophagy is a multi-functional, intracellular process that eukaryotic cells use to maintain intracellular homeostasis. The core autophagy machinery executes several steps that eventually lead to the sequestration of the targeted cellular components within double-membrane autophagosomes which subsequently fuse with lysosomes to degrade the cargo (Shibutani and Yoshimori, 2014). Autophagy is often involved in the removal of old or damaged organelles, mis-folded proteins or toxin-conjugating elements (Rogov et al., 2014). Recent research has found that autophagy is associated with the host immune system to act against invading bacteria. Induction of autophagy might directly target bacteria in phagosomes or ‘free’ in the cytosol, or indirectly trigger the innate immune responses, including inflammation, in order to obtain the maximum bactericidal activity (Huang and Brumell, 2014). However, some bacterial pathogens, for example Shigella flexneri and Listeria monocytogenes, have evolved strategies to avoid autophagy or manipulate the autophagic process to facilitate survival. The fate of B. pseudomallei after escaping from phagosomes and its interactions with the host autophagic system are yet to be fully clarified. Cullinane et al. (2008) provided evidence that lack of bacterial BopA, a type III secretion system cluster 3 (T3SS-3) effector, increased the proportion of bacteria co-localised with LC3. Electron microscopy analysis of infected macrophage cell sections demonstrated that intracellular BopA mutant bacteria are located within single-membrane phagosomes rather than double-membrane autophagosomes, indicating that LC3 is recruited directly to the phagosomes, and the bacteria are subject to LC3-associated phagocytosis (LAP) (Gong et al., 2011). Furthermore, bacteria that have escaped from phagosomes are not then targeted by canonical macroautophagy. BopA shows 23% homology with IcsB of S. flexneri, which is employed in a particular system that involves competitive binding between bacterial IcsB and the host Atg5 to the bacterial surface protein IcsA, to avoid autophagy of targeted bacteria (Ogawa and Sasakawa, 2006). Nevertheless, BopA does not act in the same way as IcsB in S. flexneri (Cullinane et…