Probiotic: is diet part of the efficacy equation?

Discovered at the beginning of the 20th century by Nobel laureate Élie Metchnikoff, probiotics have more recently emerged as a potential noninvasive therapeutic approach for the treatment of various chronic diseases. However, recent population-based clinical studies suggest that probiotics are often ineffective and may even exhibit potential deleterious effects. Hence, a deeper molecular understanding of strain-specific beneficial effects, together with the identification of endogenous/exogenous factors modulating probiotic efficacy, is needed. The lack of consistency in probiotic efficacy, together with the observation that numerous preclinical findings on probiotics are not translating once applied to humans through clinical trials, suggests a central role for environmental factors, such as dietary patterns, in probiotic efficacy. Two recent studies have been instrumental in filling this knowledge gap, defining the role played by diet in probiotic efficacy on metabolic deregulations in both mouse models and humans

Mécanismes moléculaires impliqués dans le cycle intracellulaire et la dissémination de Francisella tularensis

Francisella tularensis is a facultative intracellular multiplying bacterium responsible for a zoonosis: tularemia. This disease manifests itself in many forms depending on the mode of entry of the bacterium and can in some severe cases lead to the death of the patient. The virulence of F. tularensis is linked to its ability to adapt and multiply in the cytoplasm of the host. Indeed, the bacterium has developed many strategies to retrieve the nutrients essential for its growth. In a first part, we were interested in the importance of the Pentose Phosphate pathway of the Francisella in its intracellular cycle. We were able to demonstrate that some enzymes of this pathway such as transketolase (tktA), ribose 5-posphate isomerase A (rpiA) and ribulose3-phosphate epimerase 3 (rpE) were essential for the initial multiplication in murine macrophages. By OMIC analyses, we were also able to show that the Pentose Phosphate pathway constitutes a major metabolic hub with numerous connections to other metabolic pathways such as the tricarboxylic acid cycle, glycolysis, gluconeogenesis or the fatty acid degradation pathway. In a second part, we were interested in the dissemination by cell-to-cell contact of F. tularensis. This major mode of dissemination has been little described and does not depend on the formation of actin tails as it is the case in other pathogens. We demonstrated that this mode of dissemination, called merocytophagy, was similar to phagocytosis and depended on caspase 1, an actor of inflammation.Francisella tularensis est une bactérie à multiplication intracellulaire facultative responsable d'une zoonose : la tularémie. Cette pathologie se manifeste sous de nombreuses formes dépendantes du mode d'entrée de la bactérie et peut, dans certains cas graves, mener à la mort du patient. In vivo, cette bactérie se multiplie essentiellement à l'intérieur des macrophages. La virulence de Francisella est liée notamment à sa capacité d'adaptation et de multiplication dans le compartiment cytoplasmique des cellules infectés. Pour cela, la bactérie a développé de nombreuses stratégies pour y récupérer les nutriments essentiels à sa croissance. Dans la première partie de cette thèse, nous nous sommes intéressés à l'importance de la voie des Pentoses Phosphates de la bactérie dans son cycle intracellulaire. Nous avons pu démontrer que certaines enzymes de cette voie telles que la transkétolase (tktA), la ribose 5-posphate isomérase A (rpiA) et le ribulose3-phosphate épimerase 3 (rpE) étaient essentielles pour la multiplication initiale dans les macrophages murins. Par des analyses multi-omiques, nous avons également pu mettre en évidence que la voie des Pentoses Phosphates constituait un « hub » métabolique majeur avec de nombreuses connexions à d'autres voies métaboliques telles que le cycle de Krebs, la glycolyse, la gluconéogénèse ou encore la voie de dégradation des acides gras. Dans une seconde partie, nous nous sommes intéressés à la dissémination par contact direct de cellule à cellule de Francisella. Ce mode de dissémination majoritaire a été peu décrit et ne dépend pas de la formation de queues d'actine comme c'est le cas chez d'autres pathogènes comme Listeria et Shigella. Nous avons démontré que ce mode de dissémination nommé merocytophagie s'apparentait à la phagocytose et dépendait de la caspase 1, un acteur de l'inflammation

Which Current and Novel Diagnostic Avenues for Bacterial Respiratory Diseases?

International audienceBacterial acute pneumonia is responsible for an extremely large burden of death worldwide and diagnosis is paramount in the management of patients. While multidrugresistant bacteria is one of the biggest health threats in the coming decades, clinicians urgently need access to novel diagnostic technologies. In this review, we will first present the already existing and largely used techniques that allow identifying pathogen-associated pneumonia. Then, we will discuss the latest and most promising technological advances that are based on connected technologies (artificial intelligencebased and Omics-based) or rapid tests, to improve the management of lung infections caused by pathogenic bacteria. We also aim to highlight the mutual benefits of fundamental and clinical studies for a better understanding of lung infections and their more efficient diagnostic management

ADP‐heptose is a newly identified pathogen‐associated molecular pattern of Shigella flexneri

International audienceDuring an infection, the detection of pathogens is mediated through the interactions between pathogen-associated molecular patterns (PAMPs) and pathogen recognition receptors. β-Heptose 1,7-bisphosphate (βHBP), an intermediate of the lipopolysaccharide (LPS) biosynthesis pathway, was recently identified as a bacterial PAMP. It was reported that βHBP sensing leads to oligomerization of TIFA proteins, a mechanism controlling NF-κB activation and pro-inflammatory gene expression. Here, we compare the ability of chemically synthesized βHBP and Shigella flexneri lysate to induce TIFA oligomerization in epithelial cells. We find that, unlike bacterial lysate, βHBP fails to initiate rapid TIFA oligomerization. It only induces delayed signaling, suggesting that βHBP must be processed intracellularly to trigger inflammation. Gene deletion and complementation analysis of the LPS biosynthesis pathway revealed that ADP-heptose is the bacterial metabolite responsible for rapid TIFA oligomerization. ADP-heptose sensing occurs down to 10-10 M. During S. flexneri infection, it results in cytokine production, a process dependent on the kinase ALPK1. Altogether, our results rule out a major role of βHBP in S. flexneri infection and identify ADP-heptose as a new bacterial PAMP