Biology subjects

Maure, A.

Publications and source records attributed to Maure, A..

3 recordsLinked to original sources

bioRxiv2024

The polysaccharide capsule of Acinetobacter baumannii affects bacterial adhesion and natural transformation

Acinetobacter baumannii is an important threat worldwide due to its ability to acquire antibiotic resistance and survive harsh conditions. The polysaccharide capsule represents a major virulence and resistance asset. How the capsular polysaccharides barrier impacts bacterial adhesion remains to be investigated in A. baumannii. We characterized capsule mutants of the commonly used AB5075 strain. We assessed how these different capsule mutants adhere to biotic (bacterial and eukaryotic cells) and abiotic surfaces (polystyrene). We confirmed our observations using modern and relevant clinical isolates characterized by different capsule types and capsulation levels. Strains with low capsulation levels systematically depicted increased adhesion compared to capsulated strains, and mucoid isolates showed minimal adhesion. These results show capsule production in A. baumannii affects adhesion to various surfaces. We also determined that the presence/absence of A. baumannii capsule influences its natural transformability. This illustrates the importance of the trade-off of capsule production in A. baumannii.

microbiology↗

bioRxiv2023

An oxadiazole-based compound potentiates anti- tuberculosis treatment by increasing host resistance via zinc poisoning

Anti-tuberculosis drugs, mostly developed over 60 years ago, combined with a poorly effective vaccine, have failed to eradicate tuberculosis. More worryingly, multi-resistant strains of Mycobacterium tuberculosis are constantly emerging. Innovative strategies are thus urgently needed to improve tuberculosis treatment. Recently, host-directed therapy has emerged as a promising strategy to be used in adjunct with existing or future antibiotics, by improving innate immunity or limiting immunopathology. Here, using high content imaging, we identified novel 1,2,4-oxadiazole-based compounds, that allow human macrophages to control MTB replication. Genome-wide gene expression analysis revealed that these molecules induced zinc remobilization inside cells, resulting in bacterial zinc intoxication. More importantly, we also demonstrated that, upon treatment with these novel compounds, M. tuberculosis became even more sensitive to anti-tuberculosis drugs, in vitro and in vivo, in a mouse model of tuberculosis. Manipulation of heavy metal homeostasis holds thus great promise to be exploited to develop host-directed therapeutic interventions.

microbiology↗

bioRxiv2019

The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection

Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the hosts immune system. Here we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed macrophages into potent bactericidal phagocytes. We found that 1,495 genes were differentially expressed in M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of genes involved in metabolism, lysosome biogenesis and activation. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including nitric oxide production, phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB (TFEB), involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections.

immunology↗