Natural genetic variation inDrosophila melanogasterreveals genes associated withCoxiella burnetiiinfection

Abstract

The gram-negative bacterium Coxiella burnetii is the causative agent of Query (Q) fever in humans and coxiellosis in livestock. Host genetics are associated with Coxiella burnetii pathogenesis both in humans and animals; however, it remains unknown if specific genes are associated with severity of infection. We employed the Drosophila Genetics Reference Panel to perform a genome-wide association study to identify host genetic variants that affect host survival to Coxiella burnetii infection. The genome-wide association study identified 64 unique variants (P < 10−5) associated with 25 candidate genes. We examined the role each candidate gene contributes to host survival during Coxiella burnetii infection using flies carrying a null mutation or RNAi knockdown of each candidate. We validated 15 of the 25 candidate genes using at least one method. This is the first report establishing involvement of many of these genes or their homologs with Coxiella burnetii susceptibility in any system. Among the validated genes, FER and tara play roles in the JAK/STAT, JNK, and decapentaplegic/TGF-β signaling pathways which are components of known innate immune responses to Coxiella burnetii infection. CG42673 and DIP-ε play roles in bacterial infection and synaptic signaling but have no previous association with Coxiella burnetii pathogenesis. Furthermore, since the mammalian ortholog of CG13404 (PLGRKT) is an important regulator of macrophage function, CG13404 could play a role in host susceptibility to Coxiella burnetii through hemocyte regulation. These insights provide a foundation for further investigation regarding the genetics of Coxiella burnetii susceptibility across a wide variety of hosts.

The genetic basis of variation in immune defense against Lysinibacillus fusiformis infection in Drosophila melanogaster

“…We next asked whether line effects correlated between DGRP infection experiments (and a few other traits). We retrieved line effects for both male and female 24 hour bacterial load and female survival post Providencia rettgeri infection [ 5 , 38 ], male and female Coxiella burnetii hazard ratio [ 77 ], female Pseudomonas entomophila enteric survival [ 78 ], male and female Pseudomonas aeruginosa survival [ 21 ], male and female Metarhizium anisopliae survival [ 21 ], Staphylococcus aureus phagocyte mobilization [ 79 ], Listeria monocytogenes bacterial load [ 80 ], Enterococcus faecalis survival [ 1 ], male aggression [ 81 ], male starvation resistance [ 31 ], pigmentation (tergite 5) [ 82 ], lifespan and fecundity [ 83 ], and weight [ 35 ]. We calculated Spearman’s rank correlations for these 20 phenotypes and grouped by non-immune, Gram-positive/fungal and Gram-negative pathogens.…”

“…We next asked whether line effects correlated between DGRP infection experiments (and a few other traits). We retrieved line effects for both male and female 24 hour bacterial load and female survival post Providencia rettgeri infection [5,38], male and female Coxiella burnetii hazard ratio [77], female Pseudomonas entomophila enteric survival [78], male and female Pseudomonas aeruginosa survival [21], male and female Metarhizium anisopliae survival [21], Staphylococcus aureus phagocyte mobilization [79], Listeria monocytogenes bacterial load [80],…”

The genetic basis of variation immune defense againstLysinibacillus fusiformisinfection inDrosophila melanogaster

“…We next asked whether line effects correlated between DGRP infection experiments (and a few other traits). We retrieved line effects for both male and female 24 hour bacterial load and female survival post Providencia rettgeri infection [5, 37], male and female Coxiella burnetii hazard ratio [67], female Pseudomonas entomophila enteric survival [68], male and female Pseudomonas aeruginosa survival [21], male and female Metarhizium anisopliae survival [21], Staphylococcus aureus phagocyte mobilization [69], Listeria monocytogenes bacterial load [70], Enterococcus faecalis survival [1], male aggression [71], male starvation resistance [30], pigmentation (tergite 5) [72], lifespan and fecundity [73], and weight [34]. We calculated Spearman’s rank correlations for these 20 phenotypes and grouped by non-immune, Gram-positive/fungal and Gram-negative pathogens.…”

Shedding Light on Inter-Individual Variability of Olfactory Circuits in Drosophila

“…This aspect is further discussed in the section “Variability at the level of olfactory sensory neurons.” The genotypic variation is also observed in other traits such as lifespan or morphological and anatomical structures (e.g., brain, wing, thorax, or eye size) ( Carreira et al, 2016 ; Buchberger et al, 2021 ). Studies using the Drosophila Genetic Reference Panel (DGRP) have found the genetic origin involved in the variation between individuals expressing specific behaviors such as flight performance ( Spierer et al, 2021 ), virgin egg retention ( Akhund-Zade et al, 2017 ), aggressive behavior, immune response against pathogens ( Guzman et al, 2021 ) as well as mating behavior ( Gaertner et al, 2015 ).…”