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Cited by 80Bacterial Genetics and BiotechnologyAntimicrobial Resistance in StaphylococcusFungal and yeast genetics research

ZntR is an autoregulatory protein and negatively regulates the chromosomal zinc resistance operon znt of Staphylococcus aureus

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Singh, Vineet K., Xiong, Anming, Usgaard, Thomas R., Chakrabarti, Swarup, Deora, Rajendar, Misra, Tapan K., Jayaswal, Radheshyam K.·1999·Molecular Microbiology
DOI 10.1046/j.1365-2958.1999.01466.x
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Abstract

A chromosomally encoded znt operon of Staphylococcus aureus consists of two consecutive putative genes designated zntR and zntA. The zntA gene encodes a transmembrane protein that facilitates extrusion of Zn 2+ and Co 2+, whereas the zntR gene encodes a putative regulatory protein that controls the expression of the znt operon. The zntR gene was amplified using the polymerase chain reaction, cloned into Escherichia coli for overexpression as His‐tagged ZntR and purified by Ni 2+‐affinity column. His‐tag‐free ZntR was purified to near homogeneity after digestion with enterokinase. Electrophoretic mobility shift assays (EMSAs) indicated that the ZntR bound to a fragment of DNA corresponding to the chromosomal znt promoter region with an affinity of about 8.0 × 10−12 M. The addition of 25 μM Zn 2+ or Co 2+ in the binding reaction completely or significantly inhibited association of ZntR with the znt promoter. DNase I footprinting assays identified a ZntR binding site encompassing 49 nucleotides in the znt promoter region that contained repeated TGAA sequences. These sequences have been proposed to be the binding sites for SmtB, a metallorepressor protein from the cyanobacterium Synechococcus, to its corresponding operator/promoter. In vitro transcription assays, using S. aureus RNA polymerase, revealed that ZntR represses transcription from the znt promoter in a concentration‐dependent fashion. The EMSAs, DNase I footprinting and in vitro transcription assays indicate that ZntR is a trans‐acting repressor protein that binds to the znt promoter region and regulates its own transcription together with that of zntA.

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  • Resistance to both zinc and cobalt is conferred by the chromosomally encoded czrAB operon in S. aureus.

    “Resistance to both zinc and cobalt is conferred by the chromosomally encoded czrAB operon, which encodes a metal-regulated transcriptional repressor (CzrA, also known as ZntR) and a CDF antiporter (CzrB, also known as ZntA) [146, 147, 203].”

    From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [203]

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  1. Dey, S., and Rosen, B.P. (1995) Mechanisms of drug trans- port in prokaryotes and eukaryotes. In Drug Transport in Antimicrobial and Anticancer Chemotherapy. Georgopapa- dakou, N.H. (ed.). New York: Dekker, pp. 103±132.
  2. Gerhardt, P., Murray, R.G.E., Woods, W.A., and Kreig, N.R. (eds). Washington, DC: American Society for Micro- biology Press, pp. 436±460.
  3. Q 1999 Blackwell Science Ltd, Molecular Microbiology, 33, 200±207 ZntR, a metalloregulatory protein of S. aureus 207 13652958, 1999, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2958.1999.01466.x by Mount Vernon Nazarene University, Wiley Online Library on [23/06/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License · DOI

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Authors
Singh, V. K., Xiong, A., Usgaard, T. R., Chakrabarti, S., Deora, R., Misra, T. K., & Jayaswal, R. K.
Affiliations
  • Illinois State University (US)
  • University of Illinois Chicago (US)
Corresponding author
Jayaswal, Radheshyam K.
ORCID
Venue
Molecular Microbiology
Publisher
Wiley
Published
1999-07
Volume
33
Issue
1
Pages
200-207
ISSN
  • 0950-382X (ISSN-L)
  • 1365-2958
DOI
10.1046/j.1365-2958.1999.01466.x
OpenAlex
W2003383600
Cited by
80
References
36
Citations by year
2026: 3 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 5
FWCI
2.29
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 974 d)
Locations
  • Molecular Microbiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • University of Illinois at Urbana-Champaign
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Staphylococcus aureus, zinc resistance, metalloregulation, transcriptional repression, ZntA, promoter binding
MeSH terms
Adenosine Triphosphatases, Bacterial Proteins, Base Sequence, Cobalt, DNA-Binding Proteins, Drug Resistance, Microbial, Escherichia coli, Molecular Sequence Data, Operon, Promoter Regions, Genetic, Protein Binding, Recombinant Fusion Proteins, Regulatory Sequences, Nucleic Acid, Repressor Proteins, Staphylococcus aureus, Transcription Factors, Zinc, Gene Expression Regulation, Bacterial, Sequence Homology, Amino Acid, DNA Footprinting, Escherichia coli Proteins

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