An ECF-type transporter scavenges heme to overcome iron-limitation in Staphylococcus lugdunensis
- University of Tübingen, Germany
- University of Groningen, Netherlands
- University of Western Ontario, Canada
- KU Leuven, Belgium
Abstract
Energy-coupling factor type (ECF-transporters) represent trace nutrient acquisition systems. Substrate binding components of ECF-transporters are membrane proteins with extraordinary affinity, allowing them to scavenge trace amounts of ligand. A number of molecules have been described as substrates of ECF-transporters, but an involvement in iron-acquisition is unknown. Host-induced iron limitation during infection represents an effective mechanism to limit bacterial proliferation. We identified the iron-regulated ECF-transporter Lha in the opportunistic bacterial pathogen Staphylococcus lugdunensis and show that the transporter is specific for heme. The recombinant substrate-specific subunit LhaS accepted heme from diverse host-derived hemoproteins. Using isogenic mutants and recombinant expression of Lha, we demonstrate that its function is independent of the canonical heme acquisition system Isd and allows proliferation on human cells as sources of nutrient iron. Our findings reveal a unique strategy of nutritional heme acquisition and provide the first example of an ECF-transporter involved in overcoming host-induced nutritional limitation.
Data availability
The datasets gained during the current study are available at Dryad Digital Repository under the doi:10.5061/dryad.fqz612jqc
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Data from: An ECF-type transporter scavenges heme to overcome iron-limitation in Staphylococcus lugdunensisDryad Digital Repository, doi:10.5061/dryad.fqz612jqc.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (HE8381/3-1)
- Simon Heilbronner
Deutsche Forschungsgemeinschaft (EXC2124)
- Simon Heilbronner
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (TOP grant 714.018.003)
- Dirk J Slotboom
Canadian Institutes of Health Research (PJT-153308)
- David E Heinrichs
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experiments were performed in strict accordance with the European Health Law of the Federation of Laboratory Animal Science Associations. The protocol was approved by the Regierungspräsidium Tübingen (IMIT1/17)
Human subjects: Human Erythrocytes were isolated from venous blood of healthy volunteers in accordance with protocols approved by the Institutional Review Board for Human Subjects at the University of Tübingen. Informed written consent was obtained from all volunteers.
Copyright
© 2020, Jochim et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An ECF-type transporter scavenges heme to overcome iron-limitation in Staphylococcus lugdunensis
eLife 9:e57322.
https://doi.org/10.7554/eLife.57322
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