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Biology subjects

De Pauw, E.

Publications and source records attributed to De Pauw, E..

4 recordsLinked to original sources

Selected clinical strains of Mycobacterium avium unlock in vivo models for NTM drug discovery programs

Mycobacterium avium pulmonary disease is an emerging global health challenge for which drug development remains limited by preclinical models that rely on laboratory strains and invasive endpoint analyses. Here, we compared recent clinical M. avium isolates with the reference strain ATCC 700898 across macrophage, Galleria mellonella, and murine infection models and evaluated longitudinal micro-computed tomography ({micro}CT) as a non-invasive tool to monitor disease progression and treatment response. While extracellular growth rates were comparable, clinical isolates demonstrated enhanced host-associated fitness and induced higher bacterial burdens and more severe pulmonary pathology in mice than the reference strain. These strain-dependent differences were detected by quantitative {micro}CT imaging. Using the hypervirulent isolate MYC_0069, we further show that clarithromycin monotherapy and standard-of-care triple therapy significantly reduced bacterial burden and lung pathology. Together, these findings establish a clinically relevant chronic M. avium model that combines clinical isolates with longitudinal imaging to enable preclinical anti-mycobacterial drug evaluation in vivo.

microbiology↗

Grapevine leaf MALDI-MS imaging reveals the localisation of a putatively identified sucrose metabolite associated to Plasmopara viticola development

Despite well-established pathways and metabolites involved in grapevine-Plasmopara viticola interaction, information on the molecules involved in the first moments of pathogen contact with the leaf surface and their specific location is still missing. To understand and localise these molecules, we analysed grapevine leaf discs infected with P. viticola with MSI. Plant material preparation was optimised, and different matrices and solvents were tested. Our data shows that trichomes hamper matrix deposition and the ion signal. Results show that putatively identified sucrose presents a higher accumulation and a non-homogeneous distribution in the infected leaf discs in comparison with the controls. This accumulation was mainly on the veins, leading to the hypothesis that sucrose metabolism is being manipulated by the development structures of P. viticola. Up to our knowledge this is the first time that the localisation of a putatively identified sucrose metabolite was shown to be associated to P. viticola infection sites.

plant biology↗

Chelator sensing and lipopeptide interplay mediates molecular interspecies interactions between soil bacilli and pseudomonads

AbstractSome bacterial species are important members of the rhizosphere microbiome and confer protection to the host plant against pathogens. However, our knowledge of the multitrophic interactions determining the ecological fitness of these biocontrol bacteria in their highly competitive natural niche is still limited. In this work, we investigated the molecular mechanisms underlying interactions between B. velezensis, considered as model plant-associated and beneficial species in the Bacillus genus, and Pseudomonas as a rhizosphere-dwelling competitor. Our data show that B. velezensis boosts its arsenal of specialized antibacterials upon the perception of the secondary siderophore enantio-pyochelin produced by phylogenetically distinct pseudomonads and some other genera. We postulate that B. velezensis has developed some chelator sensing systems to learn about the identity of its surrounding competitors. Illustrating the multifaceted molecular response of Bacillus, surfactin is another crucial component of the secondary metabolome mobilized in interbacteria competition. Its accumulation not only enhances motility but, unexpectedly, the lipopeptide also acts as a chemical trap that reduces the toxicity of other lipopeptides released by Pseudomonas challengers. This in turn favors the persistence of Bacillus populations upon competitive root colonization. Our work thus highlights new ecological roles for bacterial secondary metabolites acting as key drivers of social interactions.

microbiology↗

Bagremycin Antibiotics and Ferroverdin iron-chelators are synthetized by the Same Gene Cluster

Biosynthetic gene clusters (BGCs) are organized groups of genes involved in the production of specialized metabolites. Typically, one BGC is responsible for the production of one or several similar compounds with bioactivities that usually only vary in terms of strength and/or specificity. Here we show that the previously described ferroverdins and bagremycins, which are families of metabolites with different bioactivities, are produced from the same BGC, whereby the fate of the biosynthetic pathway depends on iron availability. Under conditions of iron depletion, the monomeric bagremycins are formed, which are amino-aromatic antibiotics resulting from the condensation of 3-amino-4-hydroxybenzoic acid with p-vinylphenol. Conversely, when iron is abundantly available, the biosynthetic pathway additionally produces a molecule based on p-vinylphenyl-3-nitroso-4-hydroxybenzoate, which complexes iron to form the trimeric ferroverdins that have anticholesterol activity. Thus our work challenges the concept that BGCs should produce a single family of molecules with one type of bioactivity, the occurrence of the different metabolites being triggered by the environmental conditions.

microbiology↗