Figure 1

Figure 1

Selective autophagy receptors Optn and p62 can compensate for each other’s loss-of-function during mycobacterial infection in zebrafish. (A). Schematic diagram showing the current model of the roles of autophagy modulator Dram1 and selective autophagy receptors Optn and p62 in defense against Mm infection in zebrafish. Dram1 is induced after pathogen recognition by Tlr-Myd88-NFκB signaling and localizes predominantly to lysosomes, where it is proposed to facilitate the fusion with autophagosomes. The ubiquitin receptors Optn and p62 mediate the selective autophagy (xenophagy) of cytosolic bacteria. Dram1, Optn and p62 have all been shown to contribute to the defense response of the zebrafish host to mycobacterial infection. (B) Overexpression of optn in p62 wildtype and mutant background. In the experimental workflow, optn mRNA was injected into p62 +/+ and -/- embryos at the one cell stage, followed by injection of 200 CFU of Mm into the blood island at 28 hpf, and assessment of bacterial burden at 4 dpi (representative images shown). Quantification shows that overexpression of optn could decrease bacterial burden independent of p62. (C) Overexpression of p62 in optn wildtype and mutant background. In the experimental workflow, p62 mRNA was injected into optn +/+ and -/- embryos at the one cell stage, followed by infection and bacterial burden assessment as in (C) (representative images shown). Quantification shows that overexpression of p62 could decrease bacterial burden independent of optn. Data are displayed as percentage difference to the control group set at 100% and are accumulated from three independent infection experiments (each data point representing an individual embryo), indicated with different colors. * p<0.05, **p<0.01,***p<0.001.