Biology subjects

Akherraz, H.

Publications and source records attributed to Akherraz, H..

5 recordsLinked to original sources

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↗

bioRxiv2022

Structure-Function analysis of Lactiplantibacillus plantarum DltE reveals D-alanylated lipoteichoic acids as direct symbiotic cues supporting Drosophila juvenile growth

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 melanogasters 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 LTAs but not WTAs 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-Ala-LTAs are direct symbiotic cues supporting intestinal peptidase expression and juvenile growth in Drosophila. Our results pave the way to probing the contribution of D-Ala-LTA to host physiology in other symbiotic models.

microbiology↗

bioRxiv2021

Intestinal GCN2 controls Drosophila systemic growth upon AA imbalance in response to Lactiplantibacillus plantarum symbiotic cues encoded by r/tRNAoperons

Symbiotic bacteria interact with their host through symbiotic cues. Here, we took advantage of the mutualism between Drosophila and Lactiplantibacillus plantarum (Lp) to investigate a novel mechanism of host-symbiont interaction. Using chemically-defined diets, we found that association with Lp improves the growth of larvae fed amino acid-imbalanced diets, even though Lp cannot produce the limiting amino acid. We show that in this context Lp supports its hosts growth through a molecular dialog that requires functional operons encoding ribosomal and transfer RNAs (r/tRNAs) in Lp and the GCN2 kinase in Drosophilas enterocytes. Our data indicate Lps r/tRNAs are packaged in extracellular vesicles and activate GCN2 in a subset of larval enterocytes, a mechanism necessary to remodel the intestinal transcriptome and ultimately to support anabolic growth. Based on our findings, we propose a novel beneficial molecular dialog between host and microbes, which relies on a non-canonical role of GCN2 as a mediator of non-nutritional symbiotic cues encoded by r/tRNA operons.

microbiology↗

bioRxiv2020

Metabolic cooperation among commensal bacteria supports Drosophila juvenile growth under nutritional stress

The gut microbiota shapes animal growth trajectory in stressful nutritional environments, but the molecular mechanisms behind such physiological benefits remain poorly understood. The gut microbiota is mostly composed of bacteria, which construct metabolic networks among themselves and with the host. Until now, how the metabolic activities of the microbiota contribute to host juvenile growth remains unknown. Here, using Drosophila as a host model, we report that two of its major bacterial partners, Lactobacillus plantarum and Acetobacter pomorum engage in a beneficial metabolic dialogue that boosts host juvenile growth despite nutritional stress. We pinpoint that lactate, produced by L. plantarum, is utilized by A. pomorum as an additional carbon source, and A. pomorum provides essential amino-acids and vitamins to L. plantarum. Such bacterial cross-feeding provisions a set of anabolic metabolites to the host, which may foster host systemic growth despite poor nutrition. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/119370v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1923739org.highwire.dtl.DTLVardef@679795org.highwire.dtl.DTLVardef@110cbecorg.highwire.dtl.DTLVardef@1bc0804_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIL. plantarum feeds lactate to A. pomorum C_LIO_LIA. pomorum supplies essential amino acids and vitamins to L. plantarum C_LIO_LIMicrobiota metabolic dialogue boosts Drosophilas larval growth C_LIO_LILactate utilization by Acetobacter releases anabolic metabolites to larvae C_LI

microbiology↗

bioRxiv2019

Commensal bacteria differentially shape the nutritional requirements of Drosophila during juvenile growth

The interplay between nutrition and the microbial communities colonizing the gastro-intestinal tract (i.e. gut microbiota) determines juvenile growth trajectory. Nutritional deficiencies trigger developmental delays, and an immature gut microbiota is a hallmark of pathologies related to childhood undernutrition. However, how commensal bacteria modulate the impact of nutrition on juvenile growth remains elusive. Here, using gnotobiotic Drosophila melanogaster larvae independently associated with two model commensal bacterial strains, Acetobacter pomorumWJL (ApWJL) and Lactobacillus plantarumNC8 (LpNC8), we performed a large-scale, systematic nutritional screen based on larval growth in 40 different and precisely controlled nutritional environments. We combined these results with genome-based metabolic network reconstruction to define the biosynthetic capacities of Drosophila germ-free (GF) larvae and its two commensal bacteria. We first established that ApWJL and LpNC8 differentially fulfills the nutritional requirements of the ex-GF larvae and parsed such difference down to individual amino acids, vitamins, other micronutrients and trace metals. We found that Drosophila commensal bacteria not only fortify the hosts diet with essential nutrients but, in specific instances, functionally compensate for host auxotrophies, by either providing a metabolic intermediate or nutrient derivative to the host or by uptaking, concentrating and sparing contaminant traces of micronutrients. Our systematic work reveals that, beyond the molecular dialogue engaged between the host and its commensal partners, Drosophila and its facultative bacterial partners establish an integrated nutritional network relying on nutrients sparing and utilization.

physiology↗