Functional and structural characterization of AntR, an Sb(III) responsive transcriptional repressor

Viswanathan, Thiruselvam; Chen, Jian; Wu, Minghan; An, Lijin; Kandavelu, P.; Sankaran, Banumathi; Radhakrishnan, Manohar; Li, Mingshun; Rosen, Barry P.

doi:10.1111/mmi.14721

Cited by 6 publications

(3 citation statements)

References 42 publications

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“…To examine the role of the conserved cysteine residues in MarR ars function, Cys36, Cys37 and Cys157 were individually altered to serine residues by site-directed mutagenesis. We used a GFP biosensor strain (33) in which AdmarR ars is under control of the ara promoter and gfp is under control of the AdmarR ars promoter; in cells expressing the C36S, C37S, C157S AdMarR ars variants, gfp expression was compared with cells expressing wild type AdMarR ars following exposure to 0, 10, 20, 30 or 40 µM As(III) (Fig. 7A).…”

Section: Resultsmentioning

confidence: 99%

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Identification of a MarR subfamily that regulates arsenic resistance genes

Yu¹,

Feng²,

Chen

et al. 2021

Preprint

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In this study, comprehensive analyses were performed to determine the function of an atypical MarR homolog. Genomic analyses showed that this marR is located in an arsenic gene island in Achromobacter sp. As-55 adjacent to an arsV gene. ArsV is a flavin-dependent monooxygenase that confers resistance to the antibiotic methylarsenite (MAs(III)), the organoarsenic compound roxarsone(III) (Rox(III)), and the inorganic antimonite (Sb(III)). Similar marR genes are widely distributed in arsenic-resistant bacteria. Phylogenetic analyses showed that these MarRs are found in operons predicted to be involved in resistance to inorganic and organic arsenic species, so the subfamily was named MarRars. MarRars orthologs have three conserved cysteine residues, which are Cys36, Cys37 and Cys157 in Achromobacter sp. As-55, mutation of which compromises the response to MAs(III)/Sb(III). GFP-fluorescent biosensor assays show that AdMarRars (MarR protein of Achromobacter deleyi As-55) responds to trivalent As(III) and Sb(III) but not to pentavalent As(V) or Sb(V). The results of RT-qPCR assays show that arsV is expressed constitutively in a marR deletion mutant, indicating that marR represses transcription of arsV. Moreover, electrophoretic mobility shift assays (EMSA) demonstrate that AdMarRars binds to the promoters of both marR and arsV in the absence of ligands and that DNA binding is relieved upon binding of As(III) and Sb(III). Our results demonstrate that AdMarRars is a novel As(III)/Sb(III)-responsive transcriptional repressor that controls expression of arsV, which confers resistance to MAs(III), Roxarsone(III) and Sb(III). AdMarRars and its orthologs form a subfamily of MarR proteins that regulate genes conferring resistance to arsenic-containing antibiotics.

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Section: Resultsmentioning

confidence: 99%

“…CV17-Zero Background pTOPO-Blunt Simple Cloning Kit was purchased from Aidlab Biotechnologies Co., Ltd (Beijing, China) for construction of deletions. Plasmids pACYC184-P marR ars - gfp and pBAD- AdmarR ars were constructed for biosensor assay (33). Primers of target genes used for RT-qPCR were designed using software Beacon designer 8.1.…”

Section: Methodsmentioning

confidence: 99%

Identification of a MarR subfamily that regulates arsenic resistance genes

Yu¹,

Feng²,

Chen

et al. 2021

Preprint

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“…Like As(III), antimonite [Sb(III)] has been proposed to affect the cellular redox balance, to disrupt enzyme function by binding to sulfhydryl groups in proteins, and to cause DNA damage [ 15 , 42 – 44 ]. Additionally, Sb(III) binding to proteins is not only associated with toxicity but also with antimony resistance in yeast and bacteria [ 39 , 45 , 46 ].…”

Section: Introduction: Chemistry and Biology Of Arsenic And Antimonymentioning

confidence: 99%

Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony

Wysocki,

Rodrigues,

Litwin

et al. 2023

Cell. Mol. Life Sci.

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Arsenic and antimony are metalloids with profound effects on biological systems and human health. Both elements are toxic to cells and organisms, and exposure is associated with several pathological conditions including cancer and neurodegenerative disorders. At the same time, arsenic- and antimony-containing compounds are used in the treatment of multiple diseases. Although these metalloids can both cause and cure disease, their modes of molecular action are incompletely understood. The past decades have seen major advances in our understanding of arsenic and antimony toxicity, emphasizing genotoxicity and proteotoxicity as key contributors to pathogenesis. In this review, we highlight mechanisms by which arsenic and antimony cause toxicity, focusing on their genotoxic and proteotoxic effects. The mechanisms used by cells to maintain proteostasis during metalloid exposure are also described. Furthermore, we address how metalloid-induced proteotoxicity may promote neurodegenerative disease and how genotoxicity and proteotoxicity may be interrelated and together contribute to proteinopathies. A deeper understanding of cellular toxicity and response mechanisms and their links to pathogenesis may promote the development of strategies for both disease prevention and treatment.

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