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Adaptation of Cupriavidus metallidurans CH34 to toxic zinc concentrations involves an uncharacterized ABC-type transporter

ABSTRACT: Cupriavidus metallidurans CH34 is a well-studied metal-resistant β-proteobacterium and contains a battery of genes involved in the resistance and processing of numerous metals. Here, we performed a directed evolution experiment to obtain derivatives adapted to grow in the presence of zinc at concentrations above the minimal inhibitory concentration for the parental strain. Genetic characterization of one derivative, CH34ZnR, which was also more resistant to cadmium, revealed seven mutations, including inactivation of glpR coding for a DeoR-type transcriptional repressor by insertion of IS1088. The latter resulted in the constitutive expression of the neighboring ABC-type transporter. GlpR and the adjacent ABC transporter are highly similar to the glycerol operon regulator and ATP-driven glycerol importer of Rhizobium leguminosarum bv. viciae VF39, respectively. Deletion of glpR or the ABC transporter and complementation of CH34ZnR with the parental glpR gene further demonstrated that loss of GlpR function, with concomitant induction of the adjacent ABC transporter, is pivotal in the observed phenotype. Moreover, addition of glycerol, presumably by glycerol-mediated reduced GlpR activity, also promoted increased zinc and cadmium resistance. Thus, the ABC-type transporter is proposed to be a new adaptation route during exposure to toxic zinc concentrations.

ORGANISM(S): Cupriavidus metallidurans CH34 Cupriavidus metallidurans

PROVIDER: GSE156826 | GEO | 2021/03/03

REPOSITORIES: GEO

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Project description:Obesity is considered as a major public health concern with strong economic and social burdens. Exposure to pollutants such as heavy metals can contribute to the development of obesity and its associated metabolic disorders, including type 2 diabetes and cardiovascular diseases. Adipose tissue is an endocrine and paracrine organ that plays a key role in the development of these diseases and is one of the main target of heavy metal accumulation. In this study, we determined by inductively coupled plasma mass spectrometry cadmium concentrations in human subcutaneous and visceral adipose tissues, ranging between 2.5 nM and 2.5 µM. We found a positive correlation between cadmium levels and age, sex and smoking status and a negative correlation between cadmium and body mass index. Based on cadmium adipose tissue concentrations found in humans, we investigated the effects of cadmium exposure, at concentrations between 1 nM and 10 µM, on adipose-derived human mesenchymal stem cells differentiated into mature adipocytes in vitro. Transcriptomic analysis highlighted that such exposure altered the expression of genes involved in trace element homeostasis and heavy metal detoxification, such as Solute Carrier Family transporters and metallothioneins. This effect correlated with zinc level alteration in cells and cellular media. Interestingly, dysregulation of zinc homeostasis and transporters has been particularly associated with the development of obesity and type 2 diabetes. Moreover, we found that cadmium exposure induces the pro-inflammatory state of the adipocytes by enhancing the expression of genes such as IL-6, IL-1B and CCL2, cytokines also induced in obesity. Finally, cadmium modulates various adipocyte functions such as the insulin response signaling pathway and lipid homeostasis. Collectively, our data identified some of the cellular mechanisms by which cadmium alters adipocyte functions, thus highlighting new facets of its potential contribution to the progression of metabolic disorders.

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Adaptation of Cupriavidus metallidurans CH34 to toxic zinc concentrations involves an uncharacterized ABC-type transporter

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