Biology subjects

Monteith, K. M.

Publications and source records attributed to Monteith, K. M..

14 recordsLinked to original sources

bioRxiv2026

Fine-scale behavioural dynamics separates adaptive sickness behaviour from injury and infection pathology

Animals commonly reduce activity during infection, but it remains unclear when such "sickness behaviours" reflect adaptive host regulation versus injury responses or pathogen-driven pathology. We combined high-resolution behavioural phenotyping with experimental partitioning of injury, immune stimulation, and live bacterial infection to dissect these effects in Drosophila melanogaster. Using an outbred fly population, we tracked individual locomotor activity at 1 minute resolution for 400 hours in males and females subjected to one of four treatments: unhandled control, septic injury with buffer, immune stimulation with heat killed Pseudomonas entomophila, or septic infection with live P. entomophila. Across the early post-challenge window, total activity diverged most strongly between the unhandled control and the challenged treatments. Fine-scale analyses revealed that immune challenge primarily reshaped the microstructure of movement: the number of activity bouts changed little, whereas active bout lengths were shorter and inactive periods were modestly prolonged, especially in females. Among infected flies, individuals that died early exhibited a collapse of bout structure, showing prolonged inactivity punctuated by brief, sometimes intense, movements, whereas longer-lived infected flies maintained patterns closer to controls. These behavioural differences were detectable in the very early stages of infection: within the first 24-hours post-infection early-dying flies had both a reduced probability of initiating movement from rest and a reduced probability of sustaining on-going activity, consistent with pathogen-induced debilitation; longer-lived infected flies showed near-normal state-transition profiles. This early suppression of activity in acutely dying males was positively associated with subsequent survival time, suggesting a contribution of adaptive restraint alongside pathology. By resolving fine-scale behaviour and state-transition dynamics, our approach clarifies which aspects of "sickness behaviour" are likely adaptive and which signal pathology.

animal behavior and cognition↗

bioRxiv2025

Evidence for Transcription and Horizontal Gene Transfer in Dipteran Germline-Restricted Chromosomes

Germline-restricted chromosomes (GRCs) constitute a unique class of chromosomes confined to reproductive cells. Arising across multiple evolutionarily distant lineages, GRCs have been identified in three insect families (non-biting midges, gall midges, and fungus gnats), each within the order Diptera. Genomic characterisation in fungus gnats has revealed GRCs to be large, gene-rich chromosomes, which, together with their persistence over millennia, implies they play important biological roles within this clade. However, transcription from these chromosomes has yet to be demonstrated, leaving key questions about their function and activity unresolved. Here, we provide the first direct evidence of GRC-linked gene expression in the fungus gnat Bradysia coprophila, integrating RNA-seq data with cytological observations across multiple developmental stages. We report that GRCs express functional genes, though overall transcription is highly limited, likely due to biological factors, such as transcriptional silencing in specific germline cell types, and technical constraints, including filtering to avoid mismapping from core chromosome paralogues. We identify 15 confidently expressed GRC-linked genes using stringent criteria, including five insect homologues of unknown function and nine resembling transposable elements, and report horizontal acquisition of a [~]290 kb bacterial-derived region on GRC2. Furthermore, we perform in vitro immunofluorescence staining and confocal microscopy, which indicate increased GRC activity in female oocytes. Overall, these findings establish GRCs in fungus gnats as transcriptionally active, albeit tightly regulated and highly dynamic, chromosomes capable of expressing both endogenous and potentially horizontally acquired genes.

genomics↗

bioRxiv2024

Maternal inheritance of primary sex ratios in the dark-winged fungus gnat Lycoriella ingenua

Sex determination mechanisms in insects are extraordinarily diverse, although most species have zygotic genotypic sex determination where sex is established by sex chromosomes upon fertilisation. Dark-winged fungus gnats (Diptera: Sciaridae) are a large and speciose family of flies where sex determination is a result of an unusual interplay of zygotic, maternal, and environmental factors. This causes some species to produce clutches of offspring that deviate considerably from the standard 1:1 Fisherian sex ratio. An early study suggested that these primary sex ratios may be heritable from mother to daughter, but this observation has not been corroborated and the genetic basis for this trait remains unknown. Other studies have found that in some species, there is an additional temperature effect on the primary sex ratio, but again the mechanism is unknown. Here, we perform sibling crosses and temperature-shift experiments in a recently isolated line of the species Lycoriella ingenua and find evidence for highly variable and heritable primary sex ratios, but no significant environmental effect. We discuss the consequences of our findings for understanding the mechanisms that produce these unusual sex ratios, and the evolution of sex determination more broadly in this clade.

evolutionary biology↗

bioRxiv2023

Mitochondrial background can explain variable costs of immune deployment

Organismal health and survival depend on the ability to mount an effective immune response against infection. Yet, immune defence may be energy-demanding, resulting in fitness costs if investment in immune function deprives other physiological processes of resources. While evidence of costly immunity resulting in reduced longevity and reproduction is common, the role of energy-producing mitochondria on the magnitude of these costs is unknown. Here we employed Drosophila melanogaster cybrid lines, where several mitochondrial genotypes (mitotypes) were introgressed onto a single nuclear genetic background, to explicitly test the role of mitochondrial variation on the costs of immune stimulation. We exposed female flies carrying one of nine distinct mitotypes to either a benign, heat-killed bacterial pathogen (stimulating immune deployment while avoiding pathology), or to a sterile control, and measured lifespan, fecundity, and locomotor activity. We observed mitotype-specific costs of immune stimulation and identified a positive genetic correlation between lifespan and the proportion of time cybrids spent moving while alive. Our results suggests that costs of immunity are highly variable depending on the mitochondrial genome, adding to a growing body of work highlighting the important role of mitochondrial variation in host-pathogen interactions.

evolutionary biology↗

bioRxiv2023

The immune regulation and epidemiological consequences of immune priming in Drosophila

Invertebrates lack the immune machinery underlying vertebrate-like acquired immunity. However, in many insects past infection by the same pathogen can prime the immune response, resulting in improved survival upon reinfection. Here, we investigated the generality, specificity and mechanistic basis of innate immune priming in the fruit fly Drosophila melanogaster when infected with the gram-negative bacterial pathogen Providencia rettgeri. We find that priming in response to P. rettgeri infection is a long-lasting and pathogen-specific response. We further explore the epidemiological consequences of immune priming and find it has the potential to curtail pathogen transmission by reducing pathogen shedding and spread. The enhanced survival of individuals previously exposed to a non-lethal bacterial inoculum coincided with a transient decrease in bacterial loads, and we provide strong evidence that the effect of priming requires the IMD-responsive antimicrobial-peptide Diptericin-B in the fat body. Further, we show that while Diptericin B is the main effector of bacterial clearance, it is not sufficient for immune priming, which requires regulation of IMD by peptidoglycan recognition proteins. This work underscores the plasticity and complexity of invertebrate responses to infection, providing novel experimental evidence for the effects of innate immune priming on population-level epidemiological outcomes.

immunology↗

bioRxiv2022

The restriction factor pastrel is associated with host vigor, viral titer, and variation in disease tolerance during Drosophila C Virus infection

Genetic variation for both resistance and disease tolerance has been described in a range of species infected with bacterial, viral and fungal pathogens. In Drosophila melanogaster, genetic variation in mortality following systemic Drosophila C Virus (DCV) infection has been shown to be driven by large effect polymorphisms in the viral restriction factor pastrel (pst). However, it is unclear if pst impacts variation in DCV titres (i.e. resistance), or if it also contributes to disease tolerance. We investigated systemic infection across a range of DCV challenge doses spanning nine orders of magnitude, in males and females of ten Drosophila Genetic Reference Panel (DGRP) lines carrying either a susceptible (S) or resistant (R) pst allele. Our results uncover among-line variation in fly survival, viral titers, and disease tolerance measured both as the ability to maintain survival (mortality tolerance) and reproduction (fecundity tolerance). We confirm the role of pst in resistance, as fly lines with the resistant (R) pst allele experienced lower viral titers, and we uncover novel effects of pst on host vigor, as flies carrying the R allele exhibited higher survival and fecundity even in the absence of infection. Finally, we found significant variation in the expression of the JAK-STAT ligand upd3 and the epigenetic regulator of JAK-STAT G9a. While G9a has been previously shown to mediate tolerance of DCV infection, we found no correlation between the expression of either upd3 or G9a on fly tolerance or resistance. Our work highlights the importance of both resistance and tolerance in viral defence.

immunology↗

bioRxiv2022

Host and pathogen drivers of infection-induced changes in social aggregation behavior

Identifying how infection modifies host behaviours that determine social contact networks is important for understanding heterogeneity in infectious disease dynamics. Here, we investigate whether group social behaviour is modified during bacterial infection in Drosophila melanogaster, an established system for behavioural genetics, according to pathogen species, infectious dose, host genetic background and sex. We find that systemic infection with four different bacterial species results in a reduction in the mean pairwise distance within infected flies, and that the extent of this change depends on the infectious dose in a pathogen-specific way. In the presence of infected conspecifics, susceptible flies also tended to aggregate throughout time, but did not show any evidence of avoiding infected flies. We also observed genetic- and sex-based variation in social aggregation, with infected female flies aggregating more closely than infected males. In general, our results confirm that bacterial infection induces changes in fruit fly behaviour across a range of pathogen species, but also highlight that these effects vary between fly genetic backgrounds and can be sex-specific. We discuss possible explanations for sex differences in social aggregation and their consequences for individual variation in pathogen transmission.

animal behavior and cognition↗

bioRxiv2021

Mitonuclear interactions affect locomotor activity and sleep in Drosophila melanogaster

Mitochondria are organelles that produce cellular energy in the form of ATP through oxidative phosphorylation, and this primary function is conserved between many taxa. Locomotion is a trait that is highly reliant on metabolic function and expected to be greatly affected by disruptions to mitochondrial performance. To this end, we aimed to examine how activity and sleep vary between Drosophila melanogaster strains with different geographic origins, how these patterns are affected by mitochondrial DNA (mtDNA) variation, and how breaking up co-evolved mito-nuclear gene combinations affect the studied activity traits. The results demonstrate that Drosophila strains from different locations differ in sleep and activity, and the extent of variation differs between sexes, females in general being more active. By comparing activity and sleep of mtDNA variants introgressed onto a common nuclear background in cytoplasmic hybrid (cybrid) strains, we establish that mtDNA variation affects both traits, sex specifically. Furthermore, by using previously published mtDNA copy number data, we detected a positive correlation between mtDNA copy number and the activity levels of the cybrid flies. Altogether, our study shows that both mtDNA variation and mitonuclear interactions affect activity and sleep patterns, highlighting the important role that both genomes play on life-history trait evolution.

genetics↗

bioRxiv2021

Mechanisms of damage prevention, signalling, and repair impact the ability of Drosophila to tolerate enteric bacterial infection

The insect gut is frequently exposed to pathogenic threats and must not only clear these potential infections, but also tolerate relatively high microbe loads. In contrast to the mechanisms that eliminate pathogens, we currently know less about the mechanisms of disease tolerance. We investigated how well-described mechanisms that either prevent, signal, control, or repair damage during infection contribute to the phenotype of disease tolerance. We established enteric infections with the bacterial pathogen Pseudomonas entomophila in transgenic lines of Drosophila melanogaster fruit flies affecting dcy (a major component of the peritrophic matrix), upd3 (a cytokine-like molecule), irc (a negative regulator of reactive oxygen species) and egfr1 (epithelial growth factor receptor). Flies lacking dcy experienced the highest susceptibility, while loss of function of either irc or upd3 reduced tolerance in both sexes. The disruption of egfr1 resulted in a severe loss in tolerance in male flies but had no substantial effect on the ability of female flies to tolerate P. entomophila infection, despite carrying greater microbe loads than males. Together, our findings provide evidence for the role of damage limitation mechanisms in disease tolerance and highlight how sex differences in these mechanisms could generate sexual dimorphism in disease tolerance.

evolutionary biology↗

bioRxiv2021

Negative regulation of IMD contributes to disease tolerance during systemic bacterial infection in Drosophila

Disease tolerance is an infection phenotype where hosts show relatively high health despite harbouring elevated pathogen loads. Variation in the ability to reduce immunopathology may explain why some hosts can tolerate higher pathogen burdens with reduced pathology. Negative immune regulation would therefore appear to be a clear candidate for a mechanism underlying disease tolerance. Here, we examined how the negative regulation of the immune deficiency (IMD) pathway affects disease tolerance in Drosophila melanogaster when infected with four doses of the gram-negative bacterial pathogen Pseudomonas entomophila. We find that while flies unable to regulate the IMD response exhibited higher expression of antimicrobial peptides and lower bacterial loads as expected, this was not accompanied by a proportional reduction in mortality. Instead, UAS-RNAi knockdown of negative regulators of IMD (pirk and caudal) substantially increased the per-pathogen-mortality in both males and females across all tested infectious doses. Our results therefore highlight that in addition to regulating an efficient pathogen clearance response, negative regulators of IMD also contribute to disease tolerance.

evolutionary biology↗

bioRxiv2021

The Jak/Stat pathway mediates disease tolerance during systemic bacterial infection in Drosophila

Disease tolerance describes an infected hosts ability to maintain health independently of the ability to clear microbe loads. The Jak/Stat pathway plays a pivotal role in humoral innate immunity by detecting tissue damage and triggering cellular renewal, making it a candidate tolerance mechanism. Here, we find that in Drosophila melanogaster infected with Pseudomonas entomophila disrupting ROS-producing dual oxidase (duox) or the negative regulator of Jak/Stat Socs36E, render male flies less tolerant. Another negative regulator of Jak/Stat, G9a - which has previously been associated with variable tolerance of viral infections - did not affect the rate of mortality with increasing microbe loads compared to flies with functional G9a, suggesting it does not affect tolerance of bacterial infection as in viral infection. Our findings highlight that ROS production and Jak/Stat signalling influence the ability of flies to tolerate bacterial infection sex-specifically and may therefore contribute to sexually dimorphic infection outcomes in Drosophila.

evolutionary biology↗

bioRxiv2020

Carry on caring: infected females maintain their level of parental care despite suffering high mortality

Parental care is a key component of an organisms reproductive strategy that is thought to trade-off with allocation towards immunity. Yet it is unclear how caring parents respond to pathogens: do infected parents reduce their amount of care as a sickness behaviour or simply from being ill, or do they prioritise their offspring by maintaining high levels of care? Here we explored the consequences of infection by the pathogen Serratia marcescens on mortality, time spent providing care, reproductive output, and expression of immune genes of female parents in the burying beetle Nicrophorus vespilloides. We compared untreated control females with infected females that were inoculated with live bacteria, immune-challenged females that were inoculated with heat-killed bacteria, and injured females that were injected with buffer. We found that infected and immune-challenged females mounted an immune response and that infected females suffered increased mortality. Nevertheless, infected and immune-challenged females maintained their normal level of care and reproductive output. There was thus no evidence that infection led to either a decrease or an increase in parental care or reproductive output. Our results show that parental care, which is generally highly flexible, can remain remarkably robust and consistent despite the elevated mortality caused by infection by pathogens. Overall, these findings suggest that infected females maintain a high level of parental care; a strategy that may ensure that offspring receive the necessary amount of care but that might be detrimental to the parents own survival or that may even facilitate disease transmission to offspring.

evolutionary biology↗

bioRxiv2017

Navigating infection risk during oviposition and larval foraging in a holometabolous insect

Deciding where to eat and raise offspring carries important fitness consequences for all animals, especially if foraging, feeding and reproduction increase the risk of exposure to pathogens. In insects with complete metamorphosis, foraging occurs mainly during the larval stage, while oviposition decisions are taken by adult-stage females. Selection for infection avoidance behaviours may therefore be developmentally uncoupled. Using a combination of experimental infections and behavioural choice assays, here we tested if Drosophila melanogaster fruit flies avoid potentially infectious environments at distinct developmental stages. When given conspecific fly carcasses as a food source, larval-stage flies did not discriminate between carcasses that were clean or infected with the pathogenic Drosophila C Virus (DCV), even though scavenging was a viable route of DCV transmission. Adult females however, discriminated between different oviposition sites, laying more eggs near a clean rather than an infectious carcass if they were healthy; DCV-infected females did not discriminate between the two environments. While potentially risky, laying eggs near potentially infectious carcasses was always preferred to sites containing only fly medium. Our findings suggest that infection avoidance can play an important role in how mothers provision their offspring, and underline the need to consider infection avoidance behaviours at multiple life-stages.

animal behavior and cognition↗

bioRxiv2017

Costs and benefits of sub-lethal Drosophila C virus infection

Viruses are major evolutionary drivers of insect immune systems. Much of our knowledge of insect immune responses derives from experimental infections using the fruit fly Drosophila melanogaster. Most experiments, however, employ lethal pathogen doses through septic injury, frequently overwhelming host physiology. While this approach has revealed a number of immune mechanisms, it is less informative about the fitness costs hosts may experience during infection in the wild. Using both systemic and oral infection routes we find that even apparently benign, sub-lethal infections with the horizontally transmitted Drosophila C Virus (DCV) can cause significant physiological and behavioral morbidity that is relevant for host fitness. We describe DCV-induced effects on fly reproductive output, digestive health, and locomotor activity, and we find that viral morbidity varies according to the concentration of pathogen inoculum, host genetic background and sex. Notably, sub-lethal DCV infection resulted in a significant increase in fly reproduction, but this effect depended on host genotype. We discuss the relevance of sub-lethal morbidity for Drosophila ecology and evolution, and more broadly, we remark on the implications of deleterious and beneficial infections for the evolution of insect immunity.

evolutionary biology↗