Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition inStaphylococcus aureus

Abstract

Sufficient access to transition metals such as iron is essential 24 for bacterial proliferation and their active limitation within host tissues effectively restricts infection. To overcome iron limitation, the invasive pathogen Staphylococcus aureus uses the iron-regulated surface determinant (Isd) system to acquire hemoglobin-derived heme. While heme transport over the cell wall is well understood, its transport over the membrane is hardly investigated. In this study, we show the heme-specific permease IsdF to be energized by the general ATPase FhuC. Additionally, we show that IsdF needs appropriate location within the membrane for functionality. The membrane of S. aureus possesses special compartments (functional membrane microdomains – FMMs) to organize membrane complexes. We show IsdF to be associated with FMMs, to directly interact with the FMM scaffolding protein flotillin A (FloA) and to co-localize with the latter on intact bacterial cells. Additionally, Isd-dependent bacterial growth required FMMs and FloA. Our study shows that Isd-dependent heme acquisition requires a highly structured cell envelope to allow coordinated transport over the cell wall and membrane and it gives the first example of a bacterial nutrient acquisition system that depends on FMMs.

Nasal commensals reduceStaphylococcus aureusproliferation by restricting siderophore availability

“…As described previously, the ∆fhuC mutant grew normally in the presence of FeSO4 but was strongly disabled in iron-limited medium even if aerobactin (a substrate of FhuBGD1) was added. Similarly, the mutant grew poorly when culture supernatants of S. aureus Δsfa or Δsbn were added as sources of SF-B or SF-A, respectively which has been described before (38). All phenotypes could be complemented by plasmid-based expression of FhuC (Fig.…”

Heme acquisition and tolerance in Gram-positive model bacteria: An orchestrated balance

“…IsdD was speculated to associated with IsdEF, its function remains to be identified [ 9 ]. S. aureus possesses special compartments, functional membrane microdomains [FMMs], for coordinating diverse cellular functions [ 27 ]. IsdF is energized by the housekeeping ATPase FhuC, and IsdF interacts with the FMM scaffolding protein flotillin A (FloA), and co-localize on the intact bacterial cells [ 27 ].…”

“…S. aureus possesses special compartments, functional membrane microdomains [FMMs], for coordinating diverse cellular functions [ 27 ]. IsdF is energized by the housekeeping ATPase FhuC, and IsdF interacts with the FMM scaffolding protein flotillin A (FloA), and co-localize on the intact bacterial cells [ 27 ]. Isd-dependent heme utilization and proliferation in S. aureus requires FMMs and floA [ 27 ].…”

“…IsdF is energized by the housekeeping ATPase FhuC, and IsdF interacts with the FMM scaffolding protein flotillin A (FloA), and co-localize on the intact bacterial cells [ 27 ]. Isd-dependent heme utilization and proliferation in S. aureus requires FMMs and floA [ 27 ].…”

Genome-scale metabolic models consistently predictin vitrocharacteristics ofCorynebacterium striatum

“…The present work addresses such problems by providing 119 a unified directory structure and a collection of directly exe-120 cutable programs within a Git-based version control system. 121 To this end, the authors use their experience gained in numer-122 ous previous projects on systems biology modeling 12,14 , soft-123 ware development 33,34 and laboratory work 35,36 to precisely 124 reconstruct and experimentally validate multiple strains in 125 parallel using currently common standard operating protocols 126 for a bacterium that remains to be studied in systems biol-127 ogy. In this work, we constructed GEMs of five C. striatum 128 model strains and used them to predict growth characteris-129 tics under defined nutritional conditions.…”