Project description:Bacteria of the genus Thiomonas are found ubiquitously in arsenic contaminated waters such as Acid Mine Drainage (AMD), where they contribute to the precipitation and the natural bioremediation of arsenic. In these environments, these bacteria have developed a large range of resistance strategies, such as biofilm formation, which is one of the most ubiquitous adaptive response observed in prokaryotes to various stresses, such as those induced in the presence of toxic compounds. This study focused on the process of biofilm formation in several Thiomonas strains isolated from the same AMD. The results obtained here show that these bacteria are all capable of forming biofilms, but the architecture and the kinetics of formation of these biofilms differ depending on whether arsenic is present in the environment and from one strain to another. Indeed, two strains favored biofilm formation, whereas three others favored motility in the presence of arsenic. In order to identify the underlying mechanisms, the patterns of expression of some genes possibly involved in the process of biofilm formation were investigated in Thiomonas sp. CB2 in the presence and absence of arsenite, using a transciptomic approach (RNAseq). The findings obtained here shed interesting light on how the formation of biofilms and the motility processes contribute to the adaptation of Thiomonas strains to extreme environments.
Project description:Although the cannabinoid CB1 receptor has been implicated in atherosclerosis, its cellspecific effects in this disease are not well understood. Here, we report that male mice with myeloid-specific Cnr1 deficiency on atherogenic background developed smaller lesions and necrotic cores than controls, while only minor genotype differences were observed in females. Male Cnr1 deficient mice showed reduced arterial monocyte recruitment and macrophage proliferation with less inflammatory phenotype. The sexspecific differences in proliferation were dependent on estrogen receptor (ER)α estradiol signaling. Kinase activity profiling revealed a CB1-dependent regulation of p53 and cyclin-dependent kinases. Transcriptomic profiling further unveiled chromatin modifications, mRNA processing and mitochondrial respiration among the key processes affected by CB1 signaling, which was supported by metabolic flux assays. Chronic administration of the peripherally-restricted CB1 antagonist JD5037 inhibited plaque progression and macrophage proliferation, but only in male mice. Finally, CNR1 expression was detectable in human carotid endarterectomy plaques and inversely correlated with proliferation, oxidative metabolism and inflammatory markers, hinting to a possible implication of CB1-dependent regulation in human pathophysiology. In conclusion, impaired macrophage CB1 signaling is atheroprotective by limiting their arterial recruitment, proliferation and inflammatory reprogramming. The importance of macrophage CB1 signaling seems to be more pronounced in male mice.