Metazoans establish mutually beneficial interactions with their resident microorganisms. However, our understanding of the microbial cues contributing to host physiology remains elusive. Previously, we identified a bacterial machinery encoded by the dlt operon involved in Drosophila melanogaster's juvenile growth promotion by Lactiplantibacillus plantarum. Here, using crystallography combined with biochemical and cellular approaches, we investigate the physiological role of an uncharacterized protein (DltE) encoded by this operon. We show that lipoteichoic acids (LTAs) but not wall teichoic acids are D-alanylated in Lactiplantibacillus plantarumNC8 cell envelope and demonstrate that DltE is a D-Ala carboxyesterase removing D-Ala from LTA. Using the mutualistic association of L. plantarumNC8 and Drosophila melanogaster as a symbiosis model, we establish that D-alanylated LTAs (D-Ala-LTAs) are direct cues supporting intestinal peptidase expression and juvenile growth in Drosophila. Our results pave the way to probing the contribution of D-Ala-LTAs to host physiology in other symbiotic models.

microbiology, infectious disease, cell wall, symbiosis, D. melanogaster, Lactiplantibacillus plantarum, lipoteichoic acids

13C NMR data:
Linkage	Residue	C1	C2	C3	C4	C5	C6
0,2,6	xDAla?	172.5	49.9	16.36
0,2	aDGlcp	98.9	72.6	74.0	70.8	70.9	66.2
0	x?Gro	66.0	76.4	66.0
	P


1H NMR data:
Linkage	Residue	H1	H2	H3	H4	H5	H6
0,2,6	xDAla?	-	4.29	1.63
0,2	aDGlcp	5.19	3.55	3.77	3.42	4.18	4.45-4.63
0	x?Gro	4.02	4.13	4.02
	P


1H/13C HSQC data:
Linkage	Residue	C1/H1	C2/H2	C3/H3	C4/H4	C5/H5	C6/H6
0,2,6	xDAla?		49.9/4.29	16.36/1.63
0,2	aDGlcp	98.9/5.19	72.6/3.55	74.0/3.77	70.8/3.42	70.9/4.18	66.2/4.45-4.63
0	x?Gro	66.0/4.02	76.4/4.13	66.0/4.02
	P

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

[*]OCC(COP([*])(=O)O)O[C@H]1O[C@H](COC(=O)[C@@H](C)N)[C@@H](O)[C@H](O)[C@H]1O

387.278 g/mol (C₁₂H₂₂R₂NO₁₁P, R = next and previous repeats, not counted in mol weight)