Enterobacteria, including Escherichia coli, bloom to high levels in the gut during inflammation and strongly contribute to the pathology of inflammatory bowel diseases. To survive in the inflamed gut, E. coli must tolerate high levels of antimicrobial compounds produced by the immune system, including toxic metals like copper and reactive chlorine oxidants such as hypochlorous acid (HOCl). Here, we show that extracellular copper is a potent detoxifier of HOCl and that the widely conserved bacterial HOCl resistance enzyme RclA, which catalyzes the reduction of copper(II) to copper(I), specifically protects E. coli against damage caused by the combination of HOCl and intracellular copper. E. coli lacking RclA was highly sensitive to HOCl when grown in the presence of copper and was defective in colonizing an animal host. Our results indicate that there is unexpected complexity in the interactions between antimicrobial toxins produced by innate immune cells and that bacterial copper status is a key determinant of HOCl resistance and suggest an important and previously unsuspected role for copper redox reactions during inflammation.
IMPORTANCE During infection and inflammation, the innate immune system uses antimicrobial compounds to control bacterial populations. These include toxic metals, like copper, and reactive oxidants, including hypochlorous acid (HOCl). We have now found that RclA, a copper(II) reductase strongly induced by HOCl in proinflammatory Escherichia coli and found in many bacteria inhabiting epithelial surfaces, is required for bacteria to resist killing by the combination of intracellular copper and HOCl and plays an important role in colonization of an animal host. This finding indicates that copper redox chemistry plays a critical and previously underappreciated role in bacterial interactions with the innate immune system.
With the increasing focus on a more personalized approach to medicine using imaging techniques to select patients for targeted treatment or theranostic strategies, interest in the development of new radionuclides is expanding. Through the development of production and radiochemistry techniques, several new radiometals are being added to the toolbox of the nuclear imaging community. 43,44g,m Sc, 52g Mn, and 45 Ti are all emerging transition metal radionuclides and will be discussed in this short review. Each of these nuclides has unique imaging characteristics and shows promise for the development of new molecular imaging agents.
Despite its prevalence in the environment, the chemistry of the Ti4+ ion has long been relegated to organic solutions or hydrolyzed TiO2 polymorphs. A knowledge gap in stabilizing molecular Ti4+ species in aqueous environments has prevented the use of this ion for various applications such as radioimaging, design of water‐compatible metal–organic frameworks (MOFs), and aqueous‐phase catalysis applications. Herein, we show a thorough thermodynamic screening of bidentate chelators with Ti4+ in aqueous solution, as well as computational and structural analyses of key compounds. In addition, the hexadentate analogues of catechol (benzene‐1,2‐diol) and deferiprone (3‐hydroxy‐1,2‐dimethyl‐4(1H)‐pyridone), TREN‐CAM and THPMe respectively, were assessed for chelation of the 45Ti isotope (t1/2=3.08 h, β+=85 %, Eβ+=439 keV) towards positron emission tomography (PET) imaging applications. Both were found to have excellent capacity for kit‐formulation, and [45Ti]Ti‐TREN‐CAM was found to have remarkable stability in vivo.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.