Abstract
BackgroundStaphylococcus 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).ResultsNo 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.ConclusionsThis 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.
Highlights
Staphylococcus lugdunensis is a coagulase-negative Staphylococcus part of the commensal skin flora but emerge as an important opportunistic pathogen
In S. aureus, the use of heme as an iron source through its iron-regulated surface determinant (Isd) system contributes to its full virulence but this has not been studied in S. lugdunensis yet [8]
Impact of iron limitation on growth of S. lugdunensis N920143 With the aim to perform comparative proteomic analyses with cells harvested at the same point of the growth curve, we first evaluated bacterial growth under different conditions
Summary
Staphylococcus lugdunensis is a coagulase-negative Staphylococcus part of the commensal skin flora but emerge as an important opportunistic pathogen. S. lugdunensis is the only CoNS that has an iron-regulated surface determinant (Isd) system for iron capture and metabolism close to that of S. aureus [5]. This Isd system allows binding of hemoglobin with subsequent removal of heme that is transported into the bacterial cytoplasm. Heme is degraded and nutrient iron is released [2] In these two Staphylococci species, the isd operon is expressed under iron deficiency conditions allowing bacteria to overcome this deficiency encountered during colonization of the host and invasive diseases [6, 7]. In S. aureus, the use of heme as an iron source through its Isd system contributes to its full virulence but this has not been studied in S. lugdunensis yet [8]
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