Remote disruption of intestinal homeostasis by Mycobacterium abscessus is detrimental to Drosophila survival

Mycobacterium abscessus (Mabs), an intracellular and opportunistic pathogen, is considered the most pathogenic fast-growing mycobacterium, and causes severe pulmonary infections in patients with cystic fibrosis. While bacterial factors contributing to its pathogenicity are well studied, the host factors and responses that worsen Mabs infection are not fully understood. Here, we report that Mabs systemic infection alters Drosophila melanogaster intestinal homeostasis. Mechanistically, Mabs remotely induces a self-damaging oxidative burst, leading to excessive differentiation of intestinal stem cells into enterocytes. We demonstrated that the subsequent increased intestinal renewal is mediated by both the Notch and JAK/STAT pathways and is deleterious to Drosophila survival. In conclusion, this work highlights that the ability of Mabs to induce an exacerbated and self-damaging response in the host contributes to its pathogenesis.