Isotope tracing reveals bacterial catabolism of host-derived glutathione during Helicobacter pylori infection.

Mammalian cells synthesize the antioxidant glutathione (GSH) to shield cellular biomolecules from oxidative damage. Certain bacteria, including the gastric pathogen Helicobacter pylori, can perturb host GSH homeostasis. H.

A microbial transporter of the dietary antioxidant ergothioneine.

Low-molecular-weight (LMW) thiols are small-molecule antioxidants required for the maintenance of intracellular redox homeostasis. However, many host-associated microbes, including the gastric pathogen Helicobacter pylori, unexpectedly lack LMW-thiol biosynthetic pathways. Using reactivity-guided metabolomics, we identified the unusual LMW thiol ergothioneine (EGT) in H.

An infection-induced oxidation site regulates legumain processing and tumor growth.

Oxidative stress is a defining feature of most cancers, including those that stem from carcinogenic infections. Reactive oxygen species can drive tumor formation, yet the molecular oxidation events that contribute to tumorigenesis are largely unknown. Here we show that inactivation of a single, redox-sensitive cysteine in the host protease legumain, which is oxidized during infection with the gastric cancer-causing bacterium Helicobacter pylori, accelerates tumor growth.

Activity-Based Protein Profiling at the Host-Pathogen Interface.

Activity-based protein profiling (ABPP) is a technique for selectively detecting reactive amino acids in complex proteomes with the aid of chemical probes. Using probes that target catalytically active enzymes, ABPP can rapidly define the functional proteome of a biological system. In recent years, this approach has been increasingly applied to globally profile enzymes active at the host-pathogen interface of microbial infections.

Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo.

Norepinephrine is a monoamine neurotransmitter with a wide repertoire of physiological roles in the peripheral and central nervous systems. There are, however, no experimental means to study functional properties of individual noradrenergic synapses in the brain. Development of new approaches for imaging synaptic neurotransmission is of fundamental importance to study specific synaptic changes that occur during learning, behavior, and pathological processes.

Toward Serotonin Fluorescent False Neurotransmitters: Development of Fluorescent Dual Serotonin and Vesicular Monoamine Transporter Substrates for Visualizing Serotonin Neurons.

Ongoing efforts in our laboratories focus on design of optical reporters known as fluorescent false neurotransmitters (FFNs) that enable the visualization of uptake into, packaging within, and release from individual monoaminergic neurons and presynaptic sites in the brain. Here, we introduce the molecular probe FFN246 as an expansion of the FFN platform to the serotonergic system. Combining the acridone fluorophore with the ethylamine recognition element of serotonin, we identified FFN54 and FFN246 as substrates for both the serotonin transporter and the vesicular monoamine transporter 2 (VMAT2).