A microbiologist in new territory
The paper in Nature Microbiology is here: http://go.nature.com/2yd8oEM
Back in 2011, a PhD student in the lab of François Leulier, made an interesting observation that germ free Drosophila developed faster if certain strains of Lactobacillus plantarum were added to a low-protein diet. This observation raised many questions and opened up several lines of research in the lab. What was going on with the fly? How does L. plantarum promote Drosophila growth when there is not enough protein to go around? What are the metabolic/genetic pathways involved? And so many more!
Two years later, as I joined the lab, a postdoc was developing a nice story that L. plantarum enhances Drosophila growth by promoting intestinal peptidase expression, thereby increasing protein digestion and amino acid levels. This was in part due to peptidoglycan recognition in the enterocytes by the PGRP/Imd/Relish signaling pathway. In the lab, there were already several drosophilists studying what was happening in the fly. As a microbiologist I was mostly interested in understanding the bacterial side of this interaction.
The first days were not easy! Coming from a microbial world I had to learn a few things that a young fly Padawan needs to master: making egg-laying cages, flipping fly stocks, dissecting fly guts and most of all keeping the flies germ-free!
Germ-free Drosophila stocks. © V. Moncorgé
We started right in my comfort zone: making a transposon insertion library of L. plantarum and we increased the level of difficulty over time. Screening the library demanded organization and a healthy stock of germ-free flies laying thousands of eggs every day for 2 months. It was all worth it! By the end of the screen we had identified a set of genes in L. plantarum whose function boosted Drosophila’s growth during chronic undernutrition. And that was when the fun begun! We built several mutant bacterial strains and tested their phenotypes on our working model. We teamed up with cell wall biochemists and imaging specialist from Institut MICALIS (France) to see the impact of the mutations on bacterial cell envelope composition and shape. Mutant cells lacked D-Alanines attached to their teichoic acids and have smaller width than the wild-type.
After that, things become more complicated for a microbiologist. It was time to understand why and how the flies responded differently to the mutant strain lacking D-Alanines.
© M. Strigini
A few (several!) gut dissections later, we came up with a model: both bacterial peptidoglycan an additional signals from D-Alanine esterification of teichoic acids are required for optimal L. plantarum mediated Drosophila growth and maturation after chronic undernutrition. So what is the additional signal? That is for a now-seasoned fly jedi like me.
Full story: https://www.nature.com/article...