Alternative measures of response to Pseudomonas aeruginosa infection in Drosophila melanogaster

Studies of invertebrate immune defence often measure genetic variation either for the fitness cost of infection or for the ability of the host to clear the parasite. These studies assume that variation in measures of resistance is related to variation in fitness costs of infection. To test this assumption, we infected strains of the fruit fly, Drosophila melanogaster, with a pathogenic bacterium. We then measured the correlation between host bacterial load and the ability to survive infection. Despite the presence of genotypic variation for both traits, bacterial load and survival post-infection were not correlated. Our results support previous arguments that individual measures of immune function and the host's ability to survive infection may be decoupled. In light of these results, we suggest that the difference between tolerance and resistance to infection, a distinction commonly found in the plant literature, may also be of value in studies of invertebrate immunity.     

Desmosomes and hemidesmosomes in the flagellate Crithidia fasciculata

Summary The flagellum of the trypanosomatid flagellate Crithidia fasciculata expands asymmetrically as it emerges from the reservoir. Where the flagellar memhrane approaches the membrane lining the reservoir, desmosomes are found. These structures are arranged in several slightly curved lines and have many features in common with vertebrate desmosomes.In cultures, the flagellates stick to each other by their flagella and form rosettes. In these bundles of cells, probable sites of adhesion between flagella, or between flagella and pieces of debris, are marked by a dense filamentous tract which passes posteriorly along the flagellum and by a thick band lying just below the flagellar membrane. It is suggested that similar adhesions are found in the insect host where the flagellate attaches itself to the gut wall.     

Flagellar wave reversal in the kinetoplastid flagellate Crithidia oncopelti

Living Crithidia oncopelti cells swim through their environment by means of tip-to-base waves on their single flagellum. The cells are able to re-orient themselves by using a short burst of asymmetrical base-to-tip waves. All points on a flagellum are capable of initiating waves. Placing a population of cells in a medium of high viscosity initially produces a large number of organisms beating in the reverse mode. An individual cell has a random "switching" behavior. Viscosity affects the frequency of forward and reverse waves in different ways. The concentration of free Ca++ ions determines the direction of wave propagation in reactivated axonemes. Calmodulin may play a role in mediating the Ca++ dependence of wave direction.     

Hybrid dysgenesis-induced response to selection in Drosophila melanogaster

In Drosophila melanogaster, the P-M and I-R systems of hybrid dysgenesis are associated with high rates of transposition of P and I elements, respectively, in the germlines of dysgenic hybrids formed by crossing females of strains without active elements to males of strains containing them. Transposition rates are not markedly accelerated in the reciprocal, nondysgenic hybrids. Previous attempts to evaluate the extent to which hybrid dysgenesis-mediated P transposition contributes to mutational variance for quantitative characters by comparing the responses to selection of P-M dysgenic and nondysgenic hybrids have given variable results. This experimental design has been extended to include an additional quantitative trait and the I-R hybrid dysgenesis system. The selection responses of lines founded from both dysgenic and nondysgenic crosses showed features that would be expected from the increase in frequency of initially rare genes with major effects on the selected traits. These results differ from those of previous experiments which showed additional selection response only in lines started from dysgenic crosses, and can be explained by the occasional occurrence of large effect transposable element-induced polygenic mutations in both dysgenic and nondysgenic selection lines. High rates of transposition in populations founded from nondysgenic crosses may account for the apparently contradictory results of the earlier selection experiments, and an explanation is proposed for its occurrence.     

Transcriptional response to alcohol exposure in Drosophila melanogaster

Background  

Alcoholism presents widespread social and human health problems. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Genetic factors that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance.     

Pre-exposure affects the olfactory response of Drosophila melanogaster to menthol

A modification of the trap assay (Woodard et al., 1989) was used to evaluate the response of Drosophila melanogaster (Meigen) to food media containing menthol. Dose-response curves for flies to mentholic foods were produced for flies that had been pre-exposed to menthol, during development and adult life, and flies that had not been exposed to menthol before the assay. Mentholic food media were less attractive to Drosophila than plain food medium. Rearing flies on a medium containing menthol reduced their aversion to some concentrations of menthol. The rearing effect was not simply due to lowered general activity levels resulting from developing in a medium containing menthol. There was a threshold concentration of menthol in the rearing medium below which we found no induced behavioural change.     

Plasticity of the landing response of Drosophila melanogaster

Summary Fruitflies (Drosophila melanogaster) may respond with landing reactions in tethered flight to unilateral progressive motion of single vertical dark stripes. The response frequency to repeated unilateral stimulation has a characteristic time course, a fast increase followed by a slower decrease. This behaviour is explained by the habituation of the input channels to a leaky integrator. The half-life of the integrated signal is in the range of 1 s. Contralateral sensitization (CoS) describes the sensitization of the landing response to unilateral stimuli by preceding contralateral stimulation. It acts by increasing the initial reactivity, which habituates. The effects of CoS are thus still obvious after 1 min of repetitive stimulation. CoS can effectively be mediated by movement stimuli as well as by flickering light. We also show that binocular rotation rather than unilateral back to front motion inhibits the landing response (in the monocular part of the visual field). The biological significance of the described temporal characteristics of the landing response system and their possible neuronal basis are discussed.Abbreviations CoS contralateral sensitization     

Immune response to Encephalitozoon cuniculi infection

Microsporidia are obligate intracellular parasites, which can cause complications in immunocompromised individuals. Very little is known about the host immune response generated against these infectious agents. Encephalitozoon cuniculi is the best studied microsporidian and the protective immune response against this parasite is mediated by cytotoxic CD8(+) T cells.     

Menin links the stress response to genome stability in Drosophila melanogaster

Background

The multiple endocrine neoplasia type I gene functions as a tumor suppressor gene in humans and mouse models. In Drosophila melanogaster, mutants of the menin gene (Mnn1) are hypersensitive to mutagens or gamma irradiation and have profound defects in the response to several stresses including heat shock, hypoxia, hyperosmolarity and oxidative stress. However, it is not known if the function of menin in the stress response contributes to genome stability. The objective of this study was to examine the role of menin in the control of the stress response and genome stability.

Methodology/Principal Findings

Using a test of loss-of-heterozygosity, we show that Drosophila strains lacking a functional Mnn1 gene or expressing a Mnn1 dsRNA display increased genome instability in response to non-lethal heat shock or hypoxia treatments. This is also true for strains lacking all Hsp70 genes, implying that a precise control of the stress response is required for genome stability. While menin is required for Hsp70 expression, the results of epistatic studies indicate that the increase in genome instability observed in Mnn1 lack-of-function mutants cannot be accounted for by mis-expression of Hsp70. Therefore, menin may promote genome stability by controlling the expression of other stress-responsive genes. In agreement with this notion, gene profiling reveals that Mnn1 is required for sustained expression of all heat shock protein genes but is dispensable for early induction of the heat shock response.

Conclusions/Significance

Mutants of the Mnn1 gene are hypersensitive to several stresses and display increased genome instability when subjected to conditions, such as heat shock, generally regarded as non-genotoxic. In this report, we describe a role for menin as a global regulator of heat shock gene expression and critical factor in the maintenance of genome integrity. Therefore, menin links the stress response to the control of genome stability in Drosophila melanogaster.     

Circadian regulation of response to oxidative stress in Drosophila melanogaster

Circadian rhythms are fundamental biological phenomena generated by molecular genetic mechanisms known as circadian clocks. There is increasing evidence that circadian synchronization of physiological and cellular processes contribute to the wellness of organisms, curbing pathologies such as cancer and premature aging. Therefore, there is a need to understand how circadian clocks orchestrate interactions between the organism’s internal processes and the environment. Here, we explore the nexus between the clock and oxidative stress susceptibility in Drosophila melanogaster. We exposed flies to acute oxidative stress induced by hydrogen peroxide (H₂O₂), and determined that mortality rates were dependent on time at which exposure occurred during the day/night cycle. The daily susceptibility rhythm was abolished in flies with a null mutation in the core clock gene period (per) abrogating clock function. Furthermore, lack of per increased susceptibility to H₂O₂ compared to wild-type flies, coinciding with enhanced generation of mitochondrial H₂O₂ and decreased catalase activity due to oxidative damage. Taken together, our data suggest that the circadian clock gene period is essential for maintaining a robust anti-oxidative defense.     

Drosophila melanogaster model for Mycobacterium abscessus infection

Mycobacterium abscessus is a human pathogen that is responsible for a broad spectrum of tissue infections and disseminated infections in immunodeficient patients. This pathogen is one of the most resistant organisms to chemotherapeutic agents. Therefore, we tested the hypothesis that the fruit fly, Drosophila melanogaster, is a genetically tractable model host for M. abscessus. In this context, we infected D. melanogaster with M. abscessus. This M. abscessus infection results in dissemination in the fly body, followed by death, which is accompanied by severe indirect flight muscle and brain damage. Our data show that M. abscessus can grow and replicate in D. melanogaster w¹¹¹⁸ and that it elicited a humoral immune response, especially of the Toll antimicrobial peptide pathway. To the best of our knowledge, this is the first report that mycobacteria induce the production of antimicrobial peptides in D. melanogaster.