Identification of zinc and Zur-regulated genes in Corynebacterium diphtheriae.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Gene Expression Regulation, Bacterial* ; Genes, Bacterial*; Bacterial Proteins/*genetics ; Corynebacterium diphtheriae/*genetics ; Zinc/*metabolism; Bacterial Proteins/metabolism ; Base Sequence ; Binding Sites ; Corynebacterium diphtheriae/growth & development ; Iron/metabolism ; Membrane Proteins/metabolism ; Multigene Family ; Mutation/genetics ; Promoter Regions, Genetic ; Transcription, Genetic

Competing Interests: The authors have declared that no competing interests exist.
Corynebacterium diphtheriae is a Gram-positive bacterial pathogen and the causative agent of diphtheria, a severe disease of the upper respiratory tract of humans. Factors required for C. diphtheriae to survive in the human host are not well defined, but likely include the acquisition of essential metals such as zinc. In C. diphtheriae, zinc-responsive global gene regulation is controlled by the Zinc Uptake Regulator (Zur), a member of the Fur-family of transcriptional regulators. In this study, we use transcriptomics to identify zinc-regulated genes in C. diphtheriae by comparing gene expression of a wild-type strain grown without and with zinc supplementation. Zur-regulated genes were identified by comparing wild-type gene expression with that of an isogenic zur mutant. We observed zinc repression of several putative surface proteins, the heme efflux system hrtBA, various ABC transporters, and the non-ribosomal peptide synthetase/polyketide synthase cluster sidAB. Furthermore, increased gene expression in response to zinc was observed for the alcohol dehydrogenase, adhA. Zinc and Zur regulation were confirmed for several genes by complementing the zur deletion and subsequent RT-qPCR analysis. We used MEME to predict Zur binding sites within the promoter regions of zinc- and Zur-regulated genes, and verified Zur binding by electrophoretic mobility shift assays. Additionally, we characterized cztA (dip1101), which encodes a putative cobalt/zinc/cadmium efflux family protein. Deletion of cztA results in increased sensitivity to zinc, but not to cobalt or cadmium. This study advances our knowledge of changes to Zur-dependent global gene expression in response to zinc in C. diphtheriae. The identification of zinc-regulated ABC transporters herein will facilitate future studies to characterize zinc transport in C. diphtheriae.

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0 (Bacterial Proteins)
0 (Membrane Proteins)
E1UOL152H7 (Iron)
J41CSQ7QDS (Zinc)

Date Created: 20190828 Date Completed: 20200303 Latest Revision: 20200303

20250114

PMC6711530

10.1371/journal.pone.0221711

31454392