SufT is required for growth of Mycobacterium smegmatis under iron limiting conditions

Author:

Tamuhla Tsaone12ORCID,Joubert Lydia34,Willemse Danicke52ORCID,Williams Monique J.26ORCID

Affiliation:

1. Present address: Department of Integrative Biomedical Sciences, Division of Computational Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

2. DST-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

3. Present address: Stanford-SLAC Cryo-EM Center, Stanford University, Stanford, USA

4. Central Analytical Facilties, Microbiology Department, Stellenbosch University, Stellenbosch, South Africa

5. Present address: Texas Biomedical Research Institute, 8715 West Military Drive, San Antonio, TX, USA

6. Present address: Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa

Abstract

Iron-sulphur (FeS) clusters are versatile cofactors required for a range of biological processes within cells. Due to the reactive nature of the constituent molecules, assembly and delivery of these cofactors requires a multi-protein machinery in vivo. In prokaryotes, SufT homologues are proposed to function in the maturation and transfer of FeS clusters to apo-proteins. This study used targeted gene deletion to investigate the role of SufT in the physiology of mycobacteria, using Mycobacterium smegmatis as a model organism. Deletion of the sufT gene in M. smegmatis had no impact on growth under standard culture conditions and did not significantly alter activity of the FeS cluster dependent enzymes succinate dehydrogenase (SDH) and aconitase (ACN). Furthermore, the ΔsufT mutant was no more sensitive than the wild-type strain to the redox cycler 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), or the anti-tuberculosis drugs isoniazid, clofazimine or rifampicin. In contrast, the ΔsufT mutant displayed a growth defect under iron limiting conditions, and an increased requirement for iron during biofilm formation. This data suggests that SufT is an accessory factor in FeS cluster biogenesis in mycobacteria which is required under conditions of iron limitation.

Funder

National Research Foundation

South African Medical Research Council

Publisher

Microbiology Society

Subject

Microbiology

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