Date of Completion
Michael A. Lynes
Cell Biology | Molecular Biology
Mammalian metallothioneins (MT) are induced by various immunomodulatory molecules and are involved in a spectrum of immune processes such as essential metal homeostasis, detoxification of certain heavy metals, inflammation, and immune cell trafficking [1-3]. A bacterial metallothionein, SmtA, shares some sequence homology with mammalian MT as well as its metal-binding capabilities . In addition to its ability to sequester heavy metals, eukaryotic MT has also been shown to scavenge free radicals such as reactive oxygen and nitrogen species (ROS, RNS), interfering with their toxic effects on cells and potentially influencing their regulatory roles in cell proliferation and differentiation [5, 6]. Over the course of a bacterial infection, innate immune cells undergo a respiratory burst where they release ROS as bactericides, during which mammalian MT protects the host cell against self-inflicted oxidative damage. We hypothesize that SmtA defends bacteria against inflammatory ROS in a manner similar to mammalian MT. We have shown (using transfected Escherichia coli) that SmtA provides protection to E. coli from some forms of oxidative stress and that SmtA can also protect E. coli when co-cultured with RAW264.7 macrophage cells. Further exploration will be necessary to determine whether SmtA provides protection against mammalian immune defense mechanisms in vivo. These initial in vitro results have provided motivation to continue these studies.
Davis, Stephanie R., "Characterizing the role of the bacterial metallothionein, SmtA, in mammalian infection" (2011). Honors Scholar Theses. Paper 178.