Biology subjects

Mauri, M.

Publications and source records attributed to Mauri, M..

5 recordsLinked to original sources

bioRxiv2025

Bacterial degradation of a plant toxin and nutrient competition with commensals trade off to constrain pathogen growth

Healthy plant leaves host both commensal bacteria, which usually do not cause harm, and opportunistic pathogens, which under the right circumstances can cause disease. Microbial and plant-derived factors can potentially govern the balance between commensals and pathogens; understanding this dynamic is crucial for developing effective biocontrol strategies. In Arabidopsis thaliana, isothiocyanates (ITCs) are toxic defense metabolites that suppress most bacteria. An important virulence factor for bacterial and fungal pathogens of A. thaliana is the ITC hydrolase SaxA, which detoxifies ITCs. To investigate microbial interactions based on SaxA-mediated ITC degradation, we used five ITC-sensitive bacterial commensals and the opportunistic pathogen Pseudomonas viridiflava 3D9 (PS). All strains were isolated from healthy A. thaliana leaves and PS degrades 4-methylsulfinylbutyl-ITC (4MSOB-ITC) with SaxA. We examined their growth in the presence of 4MSOB-ITC, both in monoculture and in coculture with PS or a saxA-deficient mutant (PSKO). Based on experimental growth data, we developed a generalizable consumer-resource mathematical model incorporating ITC toxicity, ITC degradation, and nutrient use. We predicted conditions and confirmed them experimentally under which SaxA not only benefits the pathogen but also indirectly favors commensal growth, which then can limit pathogen proliferation by competing for nutrients. In addition, we tested in silico how commensal ITC susceptibility, pathogen ITC degradation rates, and growth parameters affect the trade-off between SaxA-mediated virulence (strong pathogen growth) and high commensal rescue (commensal growth). Our findings suggest that the effects of microbial traits - traditionally viewed as either virulence or plant-beneficial factors - are context-dependent. This underscores the need to reconsider how such traits are classified in the context of plant-microbiome interactions. Author SummaryHealthy plant leaves host a variety of bacteria; these can be beneficial, but some (opportunistic pathogens) can also be harmful under certain conditions. To design effective biocontrol strategies to sustainably protect plants, it is important to understand how opportunistic pathogens thrive as part of a healthy, balanced leaf microbiome. Plant defense metabolites such as isothiocyanates (ITCs) and bacterial ITC resistance mechanisms such as the ITC hydrolase SaxA may play key roles in maintaining this balance. In this study, we explore how SaxA-mediated ITC degradation by a pathogen also benefits diverse ITC-sensitive commensals and how this in turn could shape microbiome stability and plant health. Using mathematical modeling based on growth data from PS with diverse commensals, we find that interaction dynamics can be explained by ITC detoxification and nutrient competition. We predict and experimentally confirm that conditions exist under which SaxA favors commensal growth so strongly that the pathogen is outcompeted for resources, thus not benefiting from its own virulence factor. Our findings suggest that the effects of microbial traits are context-dependent, especially when functioning as public good in a community context like SaxA. Taken together, quantitative modeling of these interactions may inform strategies to maintain healthy plant microbiomes and control disease.

microbiology↗

bioRxiv2024

Hemogenic endothelium of the vitelline and umbilical arteries is the major contributor to mouse fetal lympho-myelopoiesis

Embryonic hematopoiesis consists of distinct waves originating in rapid succession from different anatomical locations. Hematopoietic progenitors appearing earlier than definitive hematopoietic stem cells (HSCs) play key roles in fetal and postnatal life. However, their precise origin, identity and the extent of their contribution need further clarification. To this aim, we took advantage of a genetic fate-mapping strategy in mice that allows labeling and tracking of distinct subsets of hemogenic endothelium (HE). Time-course labeling of hematopoietic progenitors emerging from HE between E8.5 and E9.5, before intra-embryonic definitive HSC generation, revealed a major fetal lympho-myeloid contribution which declined in the adult. Lineage tracing coupled with whole-mount imaging and single-cell RNA sequencing located its source within hematopoietic clusters of vitelline and umbilical arteries. Functional assays confirmed the transient nature of these progenitors. We therefore unveiled a hitherto unidentified early wave of fetal-restricted hematopoietic stem/progenitor cells poised for differentiation that provide a major contribution to pre-natal hematopoiesis.

developmental biology↗

bioRxiv2024

Surface versus volume synthesis governs growth-dependent efficacy of a β-lactam antibiotic

The efficacy of {beta}-lactam antibiotics depends strongly on bacterial growth rate. This can lead to poor correlation between in vivo action and in vitro assays, hindering effective prescribing - yet the mechanisms underlying growth-rate dependent {beta}-lactam action remain unclear. Here, we investigate growth-rate dependent action of mecillinam, a {beta}-lactam that targets the elongation-mediating PBP2 peptidoglycan transpeptidase enzyme, on Escherichia coli cells. We show that mecillinam alters the balance between the rates of cell surface area and volume synthesis in a growth-rate dependent manner. Under mecillinam treatment, cell volume increases exponentially at a rate [fi]xed by the growth medium, but the cells ability to produce new surface area is compromised by the antibiotic. On rich medium, this imbalance leads to lysis, but on poor medium, slow-growing cells reach a new balance between surface area and volume synthesis, allowing sustained growth even at concentrations of mecillinam far above the EUCAST MIC value. A mathematical model based on surface area vs volume synthesis can quantitatively explain growth-medium dependent differences in mecillinam killing, as well as rescue from killing when cell morphology is perturbed in a microfluidic device. {beta}-lactam antibiotic action is mechanistically complex, yet our work suggests that simple conceptual principles can help understand the interplay between molecular mechanism and cell physiology, potentially contributing to more effective use of these drugs.

microbiology↗

bioRxiv2021

Large-scale analysis of synonymous viral variants reveals global adaptation of the SARS-CoV-2 to the human codon usage

Many large national and transnational studies have been dedicated to the analysis of SARS-CoV-2 genome, most of which focused on missense and nonsense mutations. However, approximately 30% of the SARS-CoV-2 variants are synonymous, therefore changing the target codon without affecting the corresponding protein sequence. By performing a large-scale analysis of sequencing data generated from almost 400,000 SARS-CoV-2 samples, we show that silent mutations increasing the similarity of viral codons to the human ones tend to fixate in the viral genome over-time. This indicates that SARS-CoV-2 codon usage is adapting to the human host, likely improving its effectiveness in using the human aminoacyl-tRNA set through the accumulation of deceitfully neutral silent mutations. One-Sentence SummarySynonymous SARS-CoV-2 mutations related to the activity of different mutational processes may positively impact viral evolution by increasing its adaptation to human codon usage.

bioinformatics↗

bioRxiv2020

Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs

Synthetic microbial consortia have been increasingly utilized in biotechnology and experimental evidence shows that suitably engineered consortia can outperform individual species in the synthesis of valuable products. Despite significant achievements, though, a quantitative understanding of the conditions that make this possible, and of the trade-offs due to the concurrent growth of multiple species, is still limited. In this work, we contribute to filling this gap by the investigation of a known prototypical synthetic consortium. A first E. coli strain, producing a heterologous protein, is sided by a second E. coli strain engineered to scavenge toxic byproducts, thus favoring the growth of the producer at the expense of diverting part of the resources to the growth of the cleaner. The simplicity of the consortium is ideal to perform an in depth-analysis and draw conclusions of more general interest. We develop a coarse-grained mathematical model that quantitatively accounts for literature data from different key growth phenotypes. Based on this, assuming growth in chemostat, we first investigate the conditions enabling stable coexistence of both strains and the effect of the metabolic load due to heterologous protein production. In these conditions, we establish when and to what extent the consortium outperforms the producer alone in terms of productivity. Finally, we show in chemostat as well as in a fed-batch scenario that gain in productivity comes at the price of a reduced yield, reflecting at the level of the consortium resource allocation trade-offs that are well-known for individual species.

systems biology↗