Requirement of Staphylococcus aureus ATP-Binding Cassette-ATPase FhuC for Iron-Restricted Growth and Evidence that It Functions with More than One Iron Transporter

In Staphylococcus aureus, fhuCBG encodes an ATP-binding cassette (ABC) transporter that is required for the transport of iron(III)-hydroxamates; mutation of either fhuB or fhuG eliminates transport. In this paper, we describe construction and characterization of an S. aureus fhuCBG deletion strain. The ΔfhuCBG::ermC mutation not only resulted in a strain that was incapable of growth on iron(III)-hydroxamates as a sole source of iron but also resulted in a strain which had a profound growth defect in iron-restricted laboratory media. The growth defect was not a result of the inability to transport iron(III)-hydroxamates since S. aureus fhuG::Tn917 and S. aureus fhuD1::Km fhuD2::Tet mutants, which are also unable to transport iron(III)-hydroxamates, do not have similar iron-restricted growth defects. Complementation experiments demonstrated that the growth defect of the ΔfhuCBG::ermC mutant was the result of the inability to express FhuC and that this was the result of an inability to transport iron complexed to the S. aureus siderophore staphylobactin. Transport of iron(III)-staphylobactin is dependent upon SirA (binding protein), SirB (permease), and SirC (permease). S. aureus expressing FhuC with a Walker A K42N mutation could not utilize iron(III)-hydroxamates or iron(III)-staphylobactin as a sole source of iron, supporting the conclusion that FhuC, as expected, functions with FhuB, FhuG, and FhuD1 or FhuD2 to transport iron(III)-hydroxamates and is the “genetically unlinked” ABC-ATPase that functions with SirA, SirB, and SirC to transport iron(III)-staphylobactin. Finally, we demonstrated that the ΔfhuCBG::ermC strain had decreased virulence in a murine kidney abscess model

Toll-like Receptor 2 Ligands on the Staphylococcal Cell Wall Downregulate Superantigen-induced T Cell Activation and Prevent Toxic Shock Syndrome

Staphylococcal superantigens are pyrogenic exotoxins that cause massive T cell activation leading to toxic shock syndrome and death. Despite the strong adaptive immune response induced by these toxins, infections by superantigen-producing staphylococci are very common clinical events. We hypothesized that this may be partly a result of staphylococcal strains having developed strategies that downregulate the T cell response to these toxins. Here we show that the human interleukin-2 response to staphylococcal superantigens is inhibited by the simultaneous presence of bacteria. Such a downregulatory effect is the result of peptidoglycan-embedded molecules binding to Toll-like receptor 2 and inducing interleukin-10 production and apoptosis of antigen-presenting cells. We corroborated these findings in vivo by showing substantial prevention of mortality after simultaneous administration of staphylococcal enterotoxin B with either heat-killed staphylococci or Staphylococcus aureus peptidoglycan in mouse models of superantigen-induced toxic shock syndrome

Photo-dynamical characterisation of the TOI-178 resonant chain

Context. The TOI-178 system consists of a nearby, late-K-dwarf with six transiting planets in the super-Earth to mini-Neptune regime, with radii ranging from to 2.9 R⊕ and orbital periods between 1.9 and 20.7 days. All the planets, but the innermost one, form a chain of Laplace resonances. The fine-tuning and fragility of such orbital configurations ensure that no significant scattering or collision event has taken place since the formation and migration of the planets in the protoplanetary disc, thereby providing important anchors for planet formation models. Aims. We aim to improve the characterisation of the architecture of this key system and, in particular, the masses and radii of its planets. In addition, since this system is one of the few resonant chains that can be characterised by both photometry and radial velocities, we propose to use it as a test bench for the robustness of the planetary mass determination with each technique. Methods. We performed a global analysis of all the available photometry from CHEOPS, TESS and NGTS, and radial velocity from ESPRESSO, using a photo-dynamical modelling of the light curve. We also tried different sets of priors on the masses and eccentricity, as well as different stellar activity models, to study their effects on the masses estimated by transit-timing variations (TTVs) and radial velocities (RVs). Results. We demonstrate how stellar activity prevents a robust mass estimation for the three outer planets using radial velocity data alone. We also show that our joint photo-dynamical and radial velocity analysis has resulted in a robust mass determination for planets c to , with precision of ~ 12% for the mass of planet c, and better than 10% for planets d to . The new precisions on the radii range from 2 to 3%. The understanding of this synergy between photometric and radial velocity measurements will be valuable for the PLATO mission. We also show that TOI-178 is indeed currently locked in the resonant configuration, librating around an equilibrium of the chain.</p