Biology subjects

Perrier, Q.

Publications and source records attributed to Perrier, Q..

3 recordsLinked to original sources

bioRxiv2026

A DltE-DltD-DltX interaction network regulates lipoteichoic acid D-alanylation in Lactiplantibacillus plantarum and symbiotic drosophila growth promotion

D-alanylation of teichoic acids is a widespread modification of Gram-positive bacterial cell envelopes that modulates resistance to environmental stresses and host interactions. Although the cytosolic steps of this pathway are well characterized, the extracellular reactions responsible for transferring D-alanine onto teichoic acids remain poorly understood. Here we investigate the role of DltD in the commensal bacterium Lactiplantibacillus plantarum. We determined the 2.3 [A] crystal structure of the extracellular catalytic domain of DltD, which adopts an SGNH-hydrolase fold with a conserved Ser-His-Asp catalytic triad. Docking analyses with lipoteichoic acids (LTA) fragments suggest that the glycerol-phosphate backbone of LTA is accommodated along a surface groove leading to the catalytic serine, with conserved residues contributing to substrate positioning. Biochemical measurements further reveal direct interactions between DltD, the acyl-carrier protein DltX, and the LTA esterase DltE. The conserved C-terminal motif of DltX binds DltD and is required for efficient D-alanylation and for L. plantarum-mediated promotion of Drosophila juvenile growth. Together, these findings support a DltX-dependent acyl-transfer mechanism and reveal an interaction network that coordinates LTA D-alanylation in a symbiotic bacterium.

biochemistry↗

bioRxiv2025

Symbiosis through lysis: prophage activation underlies Lactiplantibacillus plantarum probiotic function

The release of bacterial bioactive molecules across the gut barrier is a crucial yet poorly understood step in microbe-host molecular dialog. Here we unravel a phage-driven mechanism that enables this process in a symbiont that supports host adaptive growth. In Lactiplantibacillus plantarum NC8 (LpNC8), we identify a stress-inducible prophage, pp2, that undergoes genotoxic-stress-dependent activation in vivo and triggers holin-lysin-mediated lysis. This controlled lytic program produces phage particles together with extracellular vesicles (EVs), enriched in symbiotic cues, including lipoteichoic acids. In a model of beneficial symbiosis, pp2-dependent lysis is strictly required for the ability of LpNC8to support juvenile growth in nutritionally challenged Drosophila melanogaster. Disruption of pp2-dependent lysis abolishes EVs release in vitro and alters the growth-promoting effect in vivo. We show that the acidic region of the Drosophila midgut, but not host antimicrobial peptides nor lysozymes, acts as a physiological trigger of prophage induction: removal of this acidic compartment markedly reduces phage production and impairs LpNC8-mediated growth promotion. These findings demonstrate that host gut physiology regulates prophage activation and reveal prophage-induced lysis as a previously unrecognized mechanism by which a beneficial gut bacterium releases symbiotic cues to support host development during nutritional stress.

microbiology↗

bioRxiv2025

Scalable 3D Bioprinting of Human Islets in a Pancreatic Decellularized Extracellular Matrix-Enriched Bioink for Beta-Cell Replacement Therapy

Allogeneic cell transplantation such as beta-cell replacement for treatment of type 1 diabetes (T1D) is constrained by poor graft survival and functionality, immune rejection, and the lack of scalable biomanufacturing processes. Here, we engineered functional human islet constructs that replicate the physiomimetic human pancreatic microenvironment by employing a clinically-scalable 3D bioprinting system. To support human islet viability and function, we developed alginate-based bioinks incorporating human pancreatic decellularized extracellular matrix (dECM). These bioink formulations were optimized for shear-thinning properties for extrusion of human islets, as well as selective permeability that supports nutrient and therapeutic molecule exchange. Extrusion-based printing parameters were refined to minimize shear stress-induced damage to human islets. The resulting bioprinted pancreatic constructs demonstrated robust structural integrity, high human islet viability (>85%), and long-term glucose-stimulated insulin secretion (GSIS) over a 21-days in vitro culture period, even at a high islet packing density (10,000 islet equivalent/mL) while free islet controls displayed a significant functional decline. The higher performance of bioprinted islets maybe attributable to the supportive 3D dECM-rich microenvironment mitigating culture-induced stress by recapitulating the islet pancreatic niche. This scalable 3D dECM-alginate bioprinted platform represents a new advanced functional material for advancing clinically translatable bio-artificial pancreas therapies for T1D.

bioengineering↗