Dgrp lines

The DGRP lines used for TWAS, listed in Dataset EV1, were obtained from the Bloomington Drosophila Stock Center. The DGRP lines used for PWAS were previously described (Okada et al, 2016). The GD and KK lines for RNAi were obtained from the Vienna Drosophila Resource Center (VDRC), which were to knock down CG7339 (VDRC_ID: 101401), CtsB1 (108315, 45345), Hsc70‐3 (101766), CG7173 (107756, 15134), Dr (110625, 7791), CG31075 (101809, 25676), CG5590 (109310, 45462), CG7519 (110613, 21652), Jafrac1 (109514), LM408 (108218, 49352), Lsp1alpha (101101), Ppn (108005, 16523), Scsalpha (107164), spirit (107936, 5497), CG14207 (31800, 31802, 44831), Top2 (30625), Tpi (25643, 25644), yip2 (26562), CG11089 (31420), Dip‐B (6296), CG33920 (103447), and CG1315 (47097). The TRiP lines for RNAi were obtained from the Bloomington Drosophila Stock Center (BDSC), which were to knock down Dr (BDSC_ID: 42891), spirit (42882), CG5590 (66929), CG31075 (50654), Jafrac1 (34971, 32498), CtsB1 (33953), CG11089 (53332, 58121), Tpi (51829), yip2 (36874), CG34015 (54031), and mCherry (35785). hh‐Gal4 was obtained from Genetic Strains Research Center, NIG, Japan.

DGRP lines are publicly available from the Bloomington stock center, IN. Raw phenotypic data for line means are presented in Table S1. Supplemental material is available at Figshare: https://doi.org/10.25387/g3.6213629.

DGRP lines were obtained from the Bloomington Stock Center and reared at room temperature on a standard fly medium. The fly medium recipe that we used is the following (for 1 l water): 6.2 g agar powder (ACROS N. 400400050), 58.8 g Farigel wheat (Westhove N. FMZH1), 58.8 g yeast (Springaline BA10), 100 ml grape juice, 4.9 ml propionic acid (Sigma N. P1386), 26.5 ml of methyl 4-hydroxybenzoate (VWR N. ALFAA14289.0) solution (400 g/l) in 95% ethanol and 1 l water. For RNAi (IR) studies, F1 progeny carrying one copy of the da-Gal4 or MyoIA-Gal4 with tub-Gal80^ts transgenes (and Diptericin-lacZ reporter in the case of da-Gal4) as well as one copy of UAS-IR (all in the w¹¹¹⁸ background) were kept at 18 °C for 3 days post eclosion, and then moved to 29 °C for 8 days to activate the UAS-IR. The UAS-Gyc76C-IR line is a gift from Julien Dow, the UAS-Nrk-IR (CG4007 R2 and R3) fly lines were obtained from the DGRC stock centre. Imd pathway mutants used are Dredd^B118 (ref. 30 (link)) and Relish^E20 (ref. 54 (link)).

DGRP lines were obtained from the Bloomington stock center and reared at room temperature on a standard fly medium. The fly medium recipe that we used is the following: 6.2-g Agar powder (ACROS N. 400400050), 58.8-g Farigel wheat (Westhove N. FMZH1), 58.8-g yeast (Springaline BA10), 100-ml grape juice, 4.9-ml Propionic acid (Sigma N. P1386), 26.5 ml of methyl 4-hydroxybenzoate (VWR N. ALFAA14289.0) solution (400 g/l) in 95% ethanol, and 1-L water. We used w¹¹¹⁸ and yw flies as wildtype. The UAS-lark RNAi line was obtained from the Transgenic RNAi Project (TRiP.JF02783), and the UAS-lark-3HA line was obtained from Bloomington stock center (stock # 7125). The P-element insertion lines in lark were obtained from Bloomington stock center (stock #15287 and #22604). Oral infection was performed using a standard protocol as in [13 ]. Survival was counted every 24 h.
For specific knockdown or overexpression of lark in the adult gut enterocyte, F1 lines carrying a copy of the MyoIA-Gal4 and tub-Gal80^ts transgenes [51 (link)], as well as one copy of either the UAS-IR or the UAS-ORF was kept at 18 °C for 3 days post-eclosion, and then moved to 29 °C for 8 days to activate the UAS transgenes. Flies were subsequently infected with P.e. using the standard oral infection protocol (OD₆₀₀ nm of 100 and 1.5% sucrose) [13 ].