Cystic fibrosis is the most common inherited lethal disease in Caucasians. It is 
caused by mutations in the cystic fibrosis transmembrane conductance regulator 
(CFTR), of which the cftr ΔF508 mutation is the most common. ΔF508 macrophages 
are intrinsically defective in autophagy because of the sequestration of 
essential autophagy molecules within unprocessed CFTR aggregates. Defective 
autophagy allows Burkholderia cenocepacia (B. cepacia) to survive and replicate 
in ΔF508 macrophages. Infection by B. cepacia poses a great risk to cystic 
fibrosis patients because it causes accelerated lung inflammation and, in some 
cases, a lethal necrotizing pneumonia. Autophagy is a cell survival mechanism 
whereby an autophagosome engulfs non-functional organelles and delivers them to 
the lysosome for degradation. The ubiquitin binding adaptor protein SQSTM1/p62 
is required for the delivery of several ubiquitinated cargos to the 
autophagosome. In WT macrophages, p62 depletion and overexpression lead to 
increased and decreased bacterial intracellular survival, respectively. In 
contrast, depletion of p62 in ΔF508 macrophages results in decreased bacterial 
survival, whereas overexpression of p62 leads to increased B. cepacia 
intracellular growth. Interestingly, the depletion of p62 from ΔF508 macrophages 
results in the release of the autophagy molecule beclin1 (BECN1) from the mutant 
CFTR aggregates and allows its redistribution and recruitment to the B. cepacia 
vacuole, mediating the acquisition of the autophagy marker LC3 and bacterial 
clearance via autophagy. These data demonstrate that p62 differentially dictates 
the fate of B. cepacia infection in WT and ΔF508 macrophages.