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Roles of TroA and TroR in Metalloregulated Growth and Gene Expression in Treponema denticola .
- Source :
-
Journal of bacteriology [J Bacteriol] 2020 Mar 11; Vol. 202 (7). Date of Electronic Publication: 2020 Mar 11 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- The availability of divalent metal cations required as cofactors for microbial metabolism is severely limited in the host environment. Bacteria have evolved highly regulated uptake systems to maintain essential metal homeostasis to meet cellular demands while preventing toxicity. The Tro operon ( troABCDR ), present in all sequenced Treponema spp., is a member of a highly conserved family of ATP-binding cassette transporters involved in metal cation uptake whose expression is controlled by TroR, a DtxR-like cation-responsive regulatory protein. Transcription of troA responds to divalent manganese and iron ( T. denticola ) or manganese and zinc ( T. pallidum ), and metal-dependent TroR binding to the troA promoter represses troA transcription. We report here the construction and complementation of defined T. denticola Δ troR and Δ troA strains to characterize (i) the role of TroA in metal-dependent T. denticola growth and (ii) the role of TroR in T. denticola gene expression. We show that TroA expression is required for T. denticola growth under iron- and manganese-limited conditions. Furthermore, TroR is required for the transcriptional regulation of troA in response to iron or manganese, and deletion of troR results in significant differential expression of more than 800 T. denticola genes in addition to troA These results suggest that (i) TroA-mediated cation uptake is important in metal homeostasis in vitro and may be important for Treponema survival in the host environment and (ii) the absence of TroR results in significant dysregulation of nearly one-third of the T. denticola genome. These effects may be direct (as with troA ) or indirect due to dysregulation of metal homeostasis. IMPORTANCE Treponema denticola is one of numerous host-associated spirochetes, a group including commensals, pathobionts, and at least one frank pathogen. While most T. denticola research concerns its role in periodontitis, its relative tractability for growth and genetic manipulation make it a useful model for studying Treponema physiology, metabolism, and host-microbe interactions. Metal micronutrient acquisition and homeostasis are highly regulated both in microbial cells and by host innate defense mechanisms that severely limit metal cation bioavailability. Here, we characterized the T. denticola troABCDR operon, the role of TroA-mediated iron and manganese uptake in growth, and the effects of TroR on global gene expression. This study contributes to our understanding of the mechanisms involved in cellular metal homeostasis required for survival in the host environment.<br /> (Copyright © 2020 American Society for Microbiology.)
- Subjects :
- ATP-Binding Cassette Transporters metabolism
Bacterial Proteins metabolism
Cations metabolism
Genetic Complementation Test
Mutagenesis
Operon
Transcription, Genetic
ATP-Binding Cassette Transporters genetics
Bacterial Proteins genetics
Gene Expression Regulation, Bacterial
Treponema denticola genetics
Treponema denticola growth & development
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5530
- Volume :
- 202
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of bacteriology
- Publication Type :
- Academic Journal
- Accession number :
- 31932313
- Full Text :
- https://doi.org/10.1128/JB.00770-19