Biology subjects

Marti, T.

Publications and source records attributed to Marti, T..

3 recordsLinked to original sources

bioRxiv2023

Legionella relative abundance in shower hose biofilms is associated with specific microbiome members

Legionella are natural inhabitants of building plumbing biofilms, where interactions with other microorganisms influence their survival, proliferation, and death. Here, we investigated the associations of Legionella with prokaryotic and eukaryotic microbiomes in biofilm samples extracted from 85 shower hoses of a multiunit residential building. Legionella spp. relative abundance in the biofilms ranged between 0 - 7.8%, of which only 0 - 0.46% was L. pneumophila. Our data suggest that some microbiome members were associated with high (e.g., Chthonomonas, Vrihiamoeba) or low (e.g., Aquabacterium, Vannella) Legionella relative abundance. The correlations of the different Legionella variants (30 Zero-Radius OTUs detected) showed distinct patterns, suggesting separate ecological niches occupied by different Legionella species. This study provides insights into the ecology of Legionella with respect to: 1) the colonization of a high number of real shower hoses biofilm samples; 2) the ecological meaning of associations between Legionella and co-occurring prokaryotic/eukaryotic organisms; 3) critical points and future directions of microbial-interaction-based-ecological-investigations.

microbiology↗

bioRxiv2023

A non-canonical function of LDHB promotes SLC7A11-mediated glutathione metabolism and protects against glutaminolysis-dependent ferroptosis in KRAS-driven lung cancer

Ferroptosis, a form of non-apoptotic cell death program driven by excessive lipid peroxidation and an important mechanism of tumor suppression, is frequently dysregulated in cancer. However, the mechanisms underlying impaired ferroptosis in oncogene-specific tumors remain poorly understood. Here we report a non- canonical role of lactate dehydrogenase B (LDHB), whose main activity is the conversion of lactate to pyruvate, in protecting KRAS-mutated lung cancer from ferroptosis. Silencing of LDHB impairs intracellular glutathione (GSH) metabolism and drives the hypersensitivity of KRAS-mutant cells to ferroptosis inducers by inhibiting the SLC7A11/GSH/GPX4 axis, a central antioxidant system against lipid peroxidation and ferroptosis by catalyzing GSH synthesis and utilization. Mechanistically, LDHB promotes SLC7A11 expression and GSH biosynthesis, and inhibition of LDHB confers metabolic synthetic lethality with ferroptosis inducers due to increased glutaminolysis and production of reactive oxygen species (ROS) in mitochondria, ultimately triggering ferroptosis of KRAS-driven lung cancer cells. Consequently, combined inhibition of LDHB and SLC7A11 synergistically suppresses tumor growth in multiple KRAS-mutant lung cancer implants and in an autochthonous model of Kras-induced lung adenocarcinoma. Taken together, our results reveal a hitherto unrecognized mechanism of ferroptosis defense by glycolytic LDHB and suggest a new strategy for the treatment of KRAS-dependent lung cancer.

cancer biology↗

bioRxiv2021

Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection

Lung-resident (LR) mesenchymal stem and stromal cells (MSCs) are key elements of the alveolar niche and fundamental regulators of homeostasis and regeneration. We interrogated their function during virus-induced lung injury using the highly prevalent respiratory syncytial virus (RSV) which causes severe outcomes in infants. We applied complementary approaches with primary pediatric LR-MSCs and a state-of-the-art model of human RSV infection in lamb. Remarkably, RSV-infection of pediatric LR-MSCs led to a robust activation, characterized by a strong antiviral and pro-inflammatory phenotype combined with mediators related to T cell function. In line with this, following in vivo infection, RSV invades and activates LR-MSCs, resulting in the expansion of the pulmonary MSC pool. Moreover, the global transcriptional response of LR-MSCs appears to follow RSV disease, switching from an early antiviral signature to repair mechanisms including differentiation, tissue remodeling, and angiogenesis. These findings demonstrate the involvement of LR-MSCs during virus-mediated acute lung injury and may have therapeutic implications. AUTHOR SUMMARYThis work identifies a novel function of lung-resident MSCs during virus-induced acute lung injury. These findings contribute to the understanding of host response and lung repair mechanisms during a highly prevalent clinical situation and may have therapeutic implications.

microbiology↗