Chromium is a prevalent toxic heavy metal, and chromate [Cr(VI)] exhibits high mutagenicity and carcinogenicity. The presence of the Cr(VI) efflux protein ChrA has been identified in strains exhibiting resistance to Cr(VI). Nevertheless, certain strains of bacteria that are resistant to Cr(VI) lack the presence of ChrB, a known regulatory factor. Here, a PadR family transcriptional repressor, ChrN, has been identified as a regulator in the response of Enterobacter sp.
Z1(CCTCC NO: M 2019147) to Cr(VI). The chrN gene is cotranscribed with the chrA gene, and the transcriptional expression of this operon is induced by Cr(VI). The binding capacity of the ChrN protein to Cr(VI) was demonstrated by both the tryptophan fluorescence assay and Ni-NTA purification assay. The interaction between ChrN and the chrAN operon promoter was validated by reporter gene assay and electrophoretic mobility shift assay. Mutation of the conserved histidine residues His14 and His50 resulted in loss of ChrN binding with the promoter of the chrAN operon. This observation implies that these residues are crucial for establishing a DNA-binding site. These findings demonstrate that ChrN functions as a transcriptional repressor, modulating the cellular response of strain Z1 to Cr(VI) exposure.
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Severe acute respiratory syndrome coronavirus 2 (SARSCoV-
2) has caused corona virus disease 2019 (COVID-19)
pandemic and led to mass casualty. Even though much effort
has been put into development of vaccine and treatment methods to combat COVID-19, no safe and efficient
cure has been discovered. Drug repurposing or drug repositioning
which is a process of investigating pre-existing drug
candidates for novel applications outside their original medical
indication can speed up the drug development process.
Raloxifene is a selective estrogen receptor modulator (SERM)
that has been approved by FDA in 1997 for treatment and
prevention of postmenopausal osteoporosis and cancer. Recently,
raloxifene demonstrates efficacy in treating viral infections
by Ebola, influenza A, and hepatitis C viruses and
shows potential for drug repurposing for the treatment of
SARS-CoV-2 infection. This review will provide an overview
of raloxifene’s mechanism of action as a SERM and present
proposed mechanisms of action in treatment of viral infections.
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