An ECF-type transporter scavenges heme to overcome iron-limitation in Staphylococcus lugdunensis

Abstract
Data availability
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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

The following data sets were generated

1. Jochim A
2. Adolf LA
3. Belikova D
4. Schilling NA
5. Setyawati I
6. Chin D
7. Meyers S
8. Verhamme P
9. Heinrichs DE
10. Slotboom DJ
11. Heilbronner S
(2020) Data from: An ECF-type transporter scavenges heme to overcome iron-limitation in Staphylococcus lugdunensis
Dryad Digital Repository, doi:10.5061/dryad.fqz612jqc.

https://doi.org/10.5061/dryad.fqz612jqc

Article and author information

Author details

Angelika Jochim

Department of Infection Biology, University of Tübingen, Tübingen, Germany

Competing interests
The authors declare that no competing interests exist.
Lea Adolf

Department of Infection Biology, University of Tübingen, Tübingen, Germany

Competing interests
The authors declare that no competing interests exist.
Darya Belikova

Department of Infection Biology, University of Tübingen, Tübingen, Germany

Competing interests
The authors declare that no competing interests exist.
Nadine Anna Schilling

Institute of Organic Chemistry, University of Tübingen, Tübingen, Germany

Competing interests
The authors declare that no competing interests exist.
Inda Setyawati

Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, Netherlands

Competing interests
The authors declare that no competing interests exist.
Denny Chin

Department of Microbiology and Immunology, University of Western Ontario, London, Canada

Competing interests
The authors declare that no competing interests exist.
Severien Meyers

Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3481-4793
Peter Verhamme

Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium

Competing interests
The authors declare that no competing interests exist.
David E Heinrichs

Department of Microbiology and Immunology, University of Western Ontario, London, Canada

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7217-2456
Dirk J Slotboom

Groningen Biomolecular and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5804-9689
Simon Heilbronner

Department of Infection Biology, University of Tübingen, Tübingen, Germany

For correspondence
simon.heilbronner@uni-tuebingen.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6774-2311

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

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.