The myeloperoxidase system of neutrophils uses hydrogen peroxide and chloride to generate hypochlorous acid, a potent bactericidal oxidant in vitro. In a mouse model of polymicrobial sepsis, we observed that mice deficient in myeloperoxidase were more likely than wild-type mice to die from infection. Mass spectrometric analysis of peritoneal inflammatory fluid from septic wild-type mice detected elevated concentrations of 3-chlorotyrosine, a characteristic end product of the myeloperoxidase system. Levels of 3-chlorotyrosine did not rise in the septic myeloperoxidase-deficient mice. Thus, myeloperoxidase seems to protect against sepsis in vivo by producing halogenating species. Surprisingly, levels of 3-bromotyrosine also were elevated in peritoneal fluid from septic wild-type mice and were markedly reduced in peritoneal fluid from septic myeloperoxidase-deficient mice. Furthermore, physiologic concentrations of bromide modulated the bactericidal effects of myeloperoxidase in vitro. It seems, therefore, that myeloperoxidase can use bromide as well as chloride to produce oxidants in vivo, even though the extracellular concentration of bromide is at least 1,000-fold lower than that of chloride. Thus, myeloperoxidase plays an important role in host defense against bacterial pathogens, and bromide might be a previously unsuspected component of this system.

Highlights d Cities possess a consistent ''core'' set of non-human microbes d Urban microbiomes echo important features of cities and city-life d Antimicrobial resistance genes are widespread in cities d Cities contain many novel bacterial and viral species

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The synthesis and characterization of four compounds formed from the reductive amination of m- and o-hydroxybenzaldehyde to (1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane)cobalt(III) are presented. These compounds are the mono- and dialkylated derivatives of the starting cobalt complex. The X-ray crystal structures of each compound, as its fully protonated chloride salt, have been obtained and are reported. The pK(a)'s of the compounds were determined by nonlinear least-squares analysis of data from potentiometric titrations and UV/vis spectrophotometry. The K(a)'s of the phenol groups of the compounds are reduced by roughly 1 order of magnitude compared to their analogous organic phenols. In the solid state, the compounds with one pendant phenol group (2, 4) are yellow and adopt the ob(3) conformation of their ethylene diamine rings in their crystal structures, while the compounds with two pendant phenol groups (3, 5) are orange and have the lel(3) conformation in their crystal structures. Solid-state reflectance UV/vis spectroscopy confirms these structural differences. In water, all four compounds form orange solutions and adopt the lel(3) conformation, as indicated by comparison of UV/vis spectroscopy and cyclic voltammetry properties with the literature.