104 Exp. Mol. Med. Vol. 44(2), 99-108, 2012 are eventually ubiquitinated, and then recognized by the autophagy machinery through recruitment of p62 (also known as SQSTM1) and LC3 (Yoshikawa et al., 2009). Notably, L. monocytogenes expressing listeriolysin O, the pore-forming cytolysin, can escape into the cytosol, where L. monocytogenes can be targeted for antibacterial autophagy (Huang and Brumell, 2009). Moreover, L. monocytogenes utilizes several virulence mechanisms to escape from host autophagy and grow slowly in specialized niches such as SLAPs, which results in the promotion of bacterial replication and chronic infection (Birmingham et al., 2008; Huang and Brumell, 2009). Recent studies by Dortet et al. have shown that L. monocytogenes hijacks the host major vault protein through interaction with InIK, a listerial virulence factor, thus resulting in escape from autophagic recognition and intracellular survival (Dortet et al., 2011). Bacterial survival and replication inside the pathogen-containing compartments: Mycobacteria, Legionella, Porphyromonas, Coxiella, and Brucella M. tuberculosis is an enormously successful intracellular pathogen that causes tuberculosis. M. tuberculosis is one of the best examples of bacterial survival and replication inside host phagocytes through escape from host immune pathways (Jo, 2010). M. tuberculosis can achieve persistent infection within the hostile environment of the macrophage through rapid transcriptional responses that counteract host immune processes, such as antigen presentation and pro-inflammatory cytokine secretion (Huynh et al., 2011). Arrest of phagosomal maturation into a phagolysosome by M. tuberculosis is a central pathway to overcome host defense and provides these bacteria with a strategy for survival in host cells (Chua et al., 2004; Huynh et al., 2011). Autophagy pathway activation induced by starvation, inhibition of mTOR pathways, vitamin D, and interferon-γ contributes to the elimi- nation of intracellular M. tuberculosis and phago- somal maturation (Gutierrez et al., 2004; Jo, 2010; Deretic, 2011). A genome-wide siRNA screening identified host factors that regulate intracellular survival of M. tuberculosis (Kumar et al., 2010). Importantly, the core host cell factors are found to be predominantly involved in the regulation of the autophagy process (Kumar et al., 2010). Recent studies showed that the M. tuberculosis eis gene negatively modulates host cell autophagy through ROS-dependent mechanisms (Shin et al., 2010a). Early activation of the autophagy response seems to be crucial for restriction of Legionella pneumophila, an intracellular bacterial pathogen responsible for an acute form of pneumonia, Legionnaire’s disease (Dubuisson and Swanson, 2006). Like M. tuberculosis, Legionella can escape from phagolysosome fusion, and perturb and delay the maturation of autophagosomes into autolyso- somes (Campoy and Colombo, 2009a; Joshi and Swanson, 2011). Various pathogens such as Porphyromonas gingivalis, Coxiella burnetii and Brucella abortus use an autophagic transit strategy during infection. These bacteria take some advantage of the autophagic pathway, in terms of intracellular survival and replication (Campoy and Colombo, 2009a). Similarly, the facultative intracellular pathogen Francisella tularensis uses a strategy to delay progression along the autophagic pathway, re- enter the endocytic pathway after cytoplasmic replication, and even hijack lysosome exocytosis to exit cells (Checroun et al., 2006; Joshi and Swanson, 2011). Future studies will elucidate more detail of the mechanisms by which bacteria interact with host autophagy pathways, which will shed light not only on bacterial pathogenesis at the molecular level but also assist in the development of new therapeutics against refractory chronic infectious diseases. Cargo receptor and autophagic targeting to bacteria Recent reports have suggested that the autophagy pathway involves selective recognition and degradation of the autophagic cargo (Johansen and Lamark, 2011). In selective autophagy, modifi- cation of target proteins or intracellular bacteria with ubiquitin is necessary for its autophagic clearance (Kirkin et al., 2009b). Autophagy receptors including p62/SQSTM1 (sequestome 1), NBR1 (neighbour of Brca1 gene) and NDP52 (nuclear dot protein 52 kDa) can simultaneously bind intracellular ubiquitinated cargos and the autophagy modifiers, such as microtubule-associated protein LC3 and γ-aminobutyric acid receptor-associated proteins (GABARAP) (Kirkin et al., 2009b; Kraft et al., 2010). Thus, autophagic receptors can mediate docking of ubiquitin-marked protein aggregates to the auto- phagosomes to induce selective autophagic de- gradation of ubiquitinated proteins, organelles, and intracellular bacteria (Kirkin et al., 2009a, 2009b; Thurston et al., 2009). As reviewed above and elsewhere (Sumpter and Levine, 2010), the cargo receptors p62 and NDP52 can target intracellular bacteria, such as S. typhimurium, S. flexneri, and L. monocytogenes, by addition of a molecular tag (such as poly- ubiquitin) to autophagic machinery (Thurston et al.,