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Arch, M.

Publications and source records attributed to Arch, M..

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The reproductive status of the host determines the tolerance and resistance to Mycobacterium marinum infection in Drosophila melanogaster

Both the sex and the reproductive status of the host have a major impact on the regulation of the immune response against infection. Due that Drosophila melanogaster has become a powerful model for study such interactions, we wanted to understand whether the sex or the reproductive status has an impact on the tolerance or resistance of the host to the in the model of systemic Mycobacterium marinum infection. We measured gene expression by RT-qPCR of immune genes, diptericin and drosomycin, as well as host survival and the bacillary load at time of death. We also assessed the impact of metabolic (by expression of upd3 and impl2) and hormonal (by ecR expression) regulation in the protection against infection. Data showed that resistance increased in actively mating males and females, and also in mated females while reducing the tolerance to infection. The data also suggest the Toll and IMD pathways determine tolerance and resistance, respectively, while basal levels of ecR favors the stimulation of the IMD pathway. A time related role has been found for upd3 expression, linked to the increase or decrease in the mycobacterial load at the beginning and at the end of the infection, respectively. Finally, impl2 expression has been related to the increase of resistance only in non-actively mating males. The results obtained allows further interpretation of the results when assessing the differences between sexes and highlights the role of the reproductive status in D. melanogaster to face infections, since our data demonstrated their importance to determine resistance and tolerance against M. marinum infection.

microbiology↗

Drosophila melanogaster is a powerful host model to study mycobacterial virulence

Drosophila melanogaster (Drosophila), the common fruit fly, is one of the most extensively studied animal models we have, with a broad, advanced, and organized research community with tools and mutants readily available at low cost. Yet, Drosophila has barely been exploited to understand the underlying mechanisms of mycobacterial infections, including those caused by the top-killer pathogen Mycobacterium tuberculosis (Mtb). In this study, we aimed to investigate whether Drosophila is a suitable host model to study mycobacterial virulence, using Mycobacterium marinum (Mmar) to model mycobacterial pathogens. First, we validated that an established mycobacterial virulence factor, EccB1 of the ESX-1 Type VII secretion system, is required for Mmar growth within the flies. Second, we identified Mmar virulence factors in Drosophila in a high-throughput genome-wide manner using transposon insertion sequencing (TnSeq). Of the 181 identified virulence genes, the vast majority (91%) had orthologs in Mtb, suggesting that the encoded virulence mechanisms may be conserved across Mmar and Mtb. Finally, we validated one of the novel Mmar virulence genes we identified, a putative ATP-binding protein ABC transporter encoded by mmar_1660, as required for full virulence during both Drosophila and human macrophage infection. Together, our results show that Drosophila is a powerful host model to study and identify novel mycobacterial virulence factors relevant to human infection.

microbiology↗