Poster abstracts

Poster number 57 submitted by Basant Abdulrahman

P62 targets Burkholderia cenocepacia to the autophagic machinery in mouse macrophages

Basant Abdulrahman (Microbial infection and immunity), Arwa Abukhweek (Microbial infection and immunity), Anwari Akhter (Microbial infection and immunity), Kyle Caution (Microbial infection and immunity), Mia Tazi (Microbial infection and immunity), Hoda Hassan (Microbial infection and immunity)

Abstract:
Burkholderia cenocepacia (B. cepacia) is an opportunistic Gram negative bacterium. It is found ubiquitously in nature, in soil and water. It represents a lethal threat to Cystic Fibrosis (CF) patients because it causes severe and persistent lung inflammation. The most common mutation in CF is ΔF508. Autophagy is a cell survival mechanism in which, an autophagosome, engulfs non-functional organelles then delivers them to the lysosome for degradation. Autophagy has been linked to a variety of disease states, including cancer and inflammation. Recently, it has been shown that autophagy plays a key role in controlling bacterial colonization, but the mechanisms of bacterial recognition by this pathway are unclear. Our data demonstrated that autophagy is defective in ΔF508 macrophages. Here, we demonstrate that an autophagy inducer, Rapamycin, markedly enhances the clearance of B. cepacia. The ubiquitin binding adaptor protein p62 is needed to deliver several types of ubiquitinated cargoes to the autophagosome. Here we show that in wild-type macrophages, p62 is required for the targeting of B. cepacia by autophagy. Thus, upon p62 knock down, the bacterial replication increased. That was accompanied by a significant decrease in the colocalization of B. cepacia with LC3 (Autophagy marker). The ΔF508 macrophages did not respond similarly to the WT macrophages showing a defect in the delivery of B. cepacia to the autophagosomes. Therefore, this study reveals that autophagy is a novel target for new drug development for CF patients to control B. cepacia infection and accompanying inflammation.

Keywords: Autophagy, p62, Burkholderia cenocepacia