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Tuesday, 5 November 2019

How do bacteria alter Drosophila behavior?

 Confronted with microorganisms that share their environment, eukaryotes have mechanisms to contain them. When this immune barrier is crossed and the animal is infected, other biological processes are triggered that limit the consequences of the infection. In a study published in the eLife journal , researchers show that Drosophila females infected with bacteria lay fewer eggs than healthy females. They provide evidence that this behavioral adaptation is due to the direct detection of a universal compound present in the bacterial wall , called peptidoglycan , by only a few neurons present in the brain of flies.

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Anyone who has been victim of a viral or bacterial infection knows the side effects that result in a loss of appetite , a fragmented sleep and, in extreme cases, a depressive state. While these "side effects" that reflect the impact of microorganisms on the host's nervous system have been clearly established, the nature of the microbial vectors of the effect and the precise identity of the targeted neurons remain, in most cases, unknown.

Figure: (Left): In the absence of infection, fertilized female Drosophila eggs. (Right): During an infection, the proliferating bacteria produce fragments of peptidoglycan, a component of their wall, in the extracellular medium. By unknown mechanisms, this compound of the bacterial wall enters the brain. Its detection by only one or two neurons (framed), of the 100,000 or so contained in the brain of a Drosophila, causes their inhibition (lowering of calcium levels) and, ultimately, a slowdown in egg deposition. It is likely that this drop in egg yield allows the infected Drosophila to allocate as much energy as possible.to fight against infection. Once infection is controlled, the level of spawning returns to normal. This is a case of behavioral immunity.
© Ambra Masuzzo.

The researchers had shown in a previous study that egg-laying behavior of fruit-infected Drosophila was modified, with infected females laying fewer eggs than their healthy counterparts. This work provided evidence that the detection of a major and universal component of the bacterial wall, the peptidoglycan, by infected Drosophila neurons alters their behavior. The next step was to identify precisely these neurons and to demonstrate how this bacterial compound could modify their activity.


In this new publication, researchers use the powergenetic and molecular tools available in Drosophila to demonstrate that by acting on only one or two of the 100,000 neurons contained in the Drosophila brain, the bacterial compound alters the behavior of the host. Using calcium imaging to measure intracellular calcium concentration, the authors demonstrate that direct application of bacterial peptidoglycan in vivo or ex vivo is sufficient to block the activity of these neurons. It remains to understand the mechanisms by which the detection of peptidoglycan and activationNF-kB signaling pathway block their activity. The cellular mechanisms that allow the peptidoglycan to reach these neurons by crossing the blood-brain barrier also remain to be elucidated.


The question now arises of the generalization of these discoveries to vertebrates . Several elements suggest that the mechanism could be conserved beyond invertebrates. On the one hand, the peptidoglycan of bacteria produced by the microbiota of mice was detected in the circulationblood and is able to cross the blood-brain barrier. In addition, mutant mice for peptidoglycan receptors exhibit behavioral disorders and social interactions. The recently published work adds an important piece to the complex puzzle that governs interactions between the microbial world and the nervous system of eukaryotes.

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