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bioRxiv · 10.1101/2021.10.29.466403

The amino acid transporter CG1139 is required for retrograde transport and fast recovery of gut enterocytes after Serratia marcescens intestinal infection

Socha, C.·Pais, I. S.·Lee, K.-Z.·Lestradet, M.·Ferrandon, D.
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Abstract

The intestinal tract is constantly exposed to microbes. Severe infections can arise following the ingestion of pathogenic microbes from contaminating food or water sources. The host directly fights off ingested pathogens with resistance mechanisms, the immune response, or withstands and repairs the damages inflicted either by virulence factors or the host immune effectors, through tolerance/resilience mechanisms. In a previous study, we reported the existence in Drosophila melanogaster of a novel evolutionarily conserved resilience mechanism to intestinal infections with a hemolysin-positive Serratia marcescens strain (SmDb11), the purge of the apical cytoplasm of enterocytes. The epithelium becomes very thin and recovers rapidly, regaining its normal thickness within several hours. Here, we found that this recovery of gut enterocyte morphology is based on the host internal reserves and not on ingested food. Indeed, we observed a retrograde transport of amino acids from the host hemolymph to the enterocytes. We have identified several amino acid transporters required for recovery and we focused on the SLC36 family transporter CG1139. CG1139 is required for the retrograde transport of amino acids. RNA sequencing revealed that genes involved in the positive regulation of growth were observed in wild-type but not CG1139 mutant guts, in which the expression of Myc and genes involved in Insulin signaling is down-regulated. Functional analysis revealed that Myc is also required for the recovery of the thick gut epithelium after infection. Altogether, our results show the importance of an amino acid transporter in the fast regrowth of the enterocytes upon infection. Unexpectedly, we found that this transporter acts non cell-autonomously and can regulate the transcription of other genes, suggesting a signaling function of CG1139 that therefore appears to act as a transceptor.

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Socha, C., Pais, I. S., Lee, K.-Z., Lestradet, M., Ferrandon, D.. 2021-10-30. The amino acid transporter CG1139 is required for retrograde transport and fast recovery of gut enterocytes after Serratia marcescens intestinal infection. https://doi.org/10.1101/2021.10.29.466403

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