The mycolic acids of Nocardia seriolae hijack Coronin-1A to inhibit autophagy for macrophage-derived foam cell formation

Nocardia seriolae alters macrophages to a “foamy” phenotype characterized by the accumulation of lipid droplets during infection to create a habitat that is ideally suited to its requirements. However, little is known about how exactly it does this. We extracted and identified specific lipids from N . seriolae , mycolic acids (NsMA), and confirmed they induced foam cells for granuloma formation in a snakehead ( Channa argus ) model. RNA-sequencing revealed that NsMA-induced foam cells were associated with Coronin-1A, which was further supported by Coronin-1A binding to NsMA as well as to the wild-type strain ZJ0503 rather than the NsMA-deficient strain Δ fadD32 . An in vitro assay revealed that the NsMA-induced Coronin-1A was responsible for inhibiting autophagy, whereas the inhibitory effect of autophagy was reversed in macrophages before receiving an anti-Coronin-1A antibody or mTOR inducer treatment. Meanwhile, the same results were also found by RNA interfering in vivo : silencing coronin-1A activated autophagy in NsMA-challenged snakehead, thereby alleviating the symptoms of granuloma formation with foam cell populations. Taken together, these results demonstrate that NsMA depends on the host's Coronin-1A to inhibit autophagy through the mTOR pathway, and thereby promotes cell foam for granuloma formation in N . seriolae -infected fish. • Extracted mycolic acids from N. seriolae induce foamy cells for granuloma formation. • The mycolic acids of N. seriolae interact with the host's Coronin-1A. • Mycolic acids hijack the host's Coronin-1A to inhibit autophagy of macrophages. • Mycolic acid-mediated granulomatous depends on the host's Coronin-1A.