Search bioRxiv⌕ Search

Biology subjects

Dussurget, O.

Publications and source records attributed to Dussurget, O..

3 recordsLinked to original sources

Dual proteomic signature of immune cells and Yersinia pestis upon blood infection

Emerging and reemerging infectious diseases represent major public health concerns. The urgent need for infection control measures requires deep understanding of molecular pathogenesis. Global approaches to study biological systems such as mass-spectrometry based proteomics benefited from groundbreaking physical and bioinformatical technological developments over recent years. However, dual proteomic study of highly pathogenic microorganisms and their hosts in complex matrices encountered during infection remains challenging due to high protein dynamic range of samples and requirements imposed in biosafety level 3 or 4 laboratories. Here, we constructed a dual proteomic pipeline of Yersinia pestis in human blood and plasma, mirroring bacteremic phase of plague. We provide the most complete Y. pestis proteome revealing a major reshaping of important bacterial path-ways such as methionine biosynthesis and iron acquisition in human plasma. Remarkably, proteomic profiling in human blood highlights a greater Yersinia outer proteins intoxication of monocytes than neutrophils. Our study unravels global expression changes and points to a specific pathogenic signature during infection, paving the way for future exploration of proteomes in the complex context of host-pathogen interactions. Subject CategoriesMicrobiology, Virology and Host Pathogen Interaction, Proteomics

systems biology↗

NAD kinase controls antibiotic susceptibility and pathogenic potential in Staphylococcus aureus

Nicotinamide adenine dinucleotide phosphate (NADPH) is the primary electron donor for reductive reactions that are essential for the biosynthesis of major cell components in all organisms. Nicotinamide adenine dinucleotide kinase (NADK) is the only enzyme that catalyzes synthesis of NADP(H) from NAD(H). While the enzymatic properties and physiological functions of NADK have been thoroughly studied, the role of NADK in bacterial pathogenesis remains unknown. Here, we used CRISPR interference to knockdown NADK gene expression to address the role of this enzyme in Staphylococcus aureus pathogenic potential. We find that NADK inhibition drastically decreases mortality of zebrafish infected with S. aureus. Further, we show that NADK promotes S. aureus survival in infected macrophages by protecting bacteria from antimicrobial defense mechanisms. Proteome-wide data analysis revealed that production of major virulence associated factors is sustained by NADK. We demonstrate that NADK is required for expression of the quorum-sensing response regulator AgrA, which controls critical S. aureus virulence determinants. These findings support a key role for NADK in bacteria survival within innate immune cells and the host during infection.

microbiology↗

Specific targeting of intestinal Prevotella copri by a Listeria monocytogenes bacteriocin

Deciphering the specific function of every microorganism in microbial gut communities is a key issue to interrogate their role during infection. Here, we report the discovery of a Listeria bacteriocin, Lmo2776, that specifically targets the abundant gut commensal Prevotella copri and affects Listeria infection. Oral infection of conventional mice with a {Delta}lmo2776 mutant leads to a thinner intestinal mucus layer and higher Listeria loads both in the intestinal content and deeper tissues compared to WT Listeria, while no difference is observed in germ-free mice. This microbiota-dependent effect is phenocopied by precolonization of germ-free mice before Listeria infection, with P. copri, but not with other commensals. Together, these data unveil a role for Prevotella in controlling intestinal infection, highlighting that pathogens may selectively deplete microbiota to avoid excessive inflammation.

microbiology↗