scholarly journals Author response: An ECF-type transporter scavenges heme to overcome iron-limitation in Staphylococcus lugdunensis

2020 ◽  
Author(s):  
Angelika Jochim ◽  
Lea Adolf ◽  
Darya Belikova ◽  
Nadine Anna Schilling ◽  
Inda Setyawati ◽  
...  

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Angelika Jochim ◽  
Lea Adolf ◽  
Darya Belikova ◽  
Nadine Anna Schilling ◽  
Inda Setyawati ◽  
...  

Energy-coupling factor type transporters (ECF) 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.



2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Marion Aubourg ◽  
Anne Dhalluin ◽  
François Gravey ◽  
Marine Pottier ◽  
Nicolas Thomy ◽  
...  

Abstract Background Staphylococcus lugdunensis is a coagulase-negative Staphylococcus part of the commensal skin flora but emerge as an important opportunistic pathogen. Because iron limitation is a crucial stress during infectious process, we performed phenotypic study and compared proteomic profiles of this species incubated in absence and in presence of the iron chelator 2,2′-dipyridyl (DIP). Results No modification of cell morphology nor cell wall thickness were observed in presence of DIP. However iron-limitation condition promoted biofilm formation and reduced the ability to cope with oxidative stress (1 mM H2O2). In addition, S. lugdunensis N920143 cultured with DIP was significantly less virulent in the larvae of Galleria mellonella model of infection than that grown under standard conditions. We verified that these phenotypes were due to an iron limitation by complementation experiments with FeSO4. By mass spectrometry after trypsin digestion, we characterized the first iron-limitation stress proteome in S. lugdunensis. Among 1426 proteins identified, 349 polypeptides were differentially expressed. 222 were more and 127 less abundant in S. lugdunensis incubated in iron-limitation condition, and by RT-qPCR, some of the corresponding genes have been shown to be transcriptionally regulated. Our data revealed that proteins involved in iron metabolism and carriers were over-expressed, as well as several ABC transporters and polypeptides linked to cell wall metabolism. Conversely, enzymes playing a role in the oxidative stress response (especially catalase) were repressed. Conclusions This phenotypic and global proteomic study allowed characterization of the response of S. lugdunensis to iron-limitation. We showed that iron-limitation promoted biofilm formation, but decrease the oxidative stress resistance that may, at least in part, explained the reduced virulence of S. lugdunensis observed under low iron condition.



Author(s):  
Marion Aubourg ◽  
François Gravey ◽  
Anne Dhalluin ◽  
Jean-Christophe Giard




2020 ◽  
Author(s):  
Gesa F. Dinges ◽  
Alexander S. Chockley ◽  
Till Bockemühl ◽  
Kei Ito ◽  
Alexander Blanke ◽  
...  


2020 ◽  
Author(s):  
Charles A. Williams ◽  
Kimberly E. Miller ◽  
Nisa P. Williams ◽  
Christine V. Portfors ◽  
David J. Perkel


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