Caught in the act: in vivo development of macrolide resistance to Campylobacter jejuni infection.

We report the first instance of macrolide resistance developing in vivo following appropriate antibiotic use in a healthy volunteer as a part of a controlled human infection with Campylobacter jejuni. In vivo development of macrolide resistance may be an important contributor to antibiotic resistance in C. jejuni.

In a randomized, double-blinded, placebo-controlled trial, the single oral dose typhoid vaccine, M01ZH09, is safe and immunogenic at doses up to 1.7 x 10(10) colony-forming units.

M01ZH09, S. Typhi (Ty2 Delta aroC Delta ssaV) ZH9, is a single oral dose typhoid vaccine with independently attenuating deletions. A phase II randomized, double-blind, placebo-controlled, dose-escalating trial evaluated the safety and immunogenicity of M01ZH09 to 1.7 x 10(10) colony-forming units (CFU). 187 Healthy adults received vaccine or placebo in four cohorts. Serologic responses and IgA ELISPOT were measured. At all doses, the vaccine was well tolerated and without bacteremias. One subject had a transient low-grade fever. 62.2-86.1% of subjects seroconverted S. Typhi-specific LPS IgG and 83.3-97.4% IgA; 92.1% had a positive S. Typhi LPS ELISPOT. M01ZH09 is safe and immunogenic up to 1.7 x 10(10)CFU. Efficacy testing of this single-dose oral typhoid vaccine is needed.

Charge transport through DNA four-way junctions.

Long range oxidative damage as a result of charge transport is shown to occur through single crossover junctions assembled from four semi-complementary strands of DNA. When a rhodium complex is tethered to one of the arms of the four-way junction assembly, thereby restricting its intercalation into the pi-stack, photo-induced oxidative damage occurs to varying degrees at all guanine doublets in the assembly, though direct strand scission only occurs at the predicted site of intercalation. In studies where the Mg(2+) concentration was varied, so as to perturb base stacking at the junction, charge transport was found to be enhanced but not to be strongly localized to the arms that preferentially stack on each other. These data suggest that the conformations of four-way junctions can be relatively mobile. Certainly, in four-way junctions charge transport is less discriminate than in the more rigidly stacked DNA double crossover assemblies.

Robust charge transport in DNA double crossover assemblies.

BACKGROUND: Multiple-stranded DNA assemblies, encoded by sequence, have been constructed in an effort to self-assemble nanodevices of defined molecular architecture. Double-helical DNA has been probed also as a molecular medium for charge transport. Conductivity studies suggest that DNA displays semiconductor properties, whereas biochemical studies have shown that oxidative damage to B-DNA at the 5'-G of a 5'-GG-3' doublet can occur by charge transport through DNA up to 20 nm from a photo-excited metallointercalator. The possible application of DNA assemblies, in particular double crossover (DX) molecules, in electrical nanodevices prompted the design of a DNA DX assembly with oxidatively sensitive guanine moieties and a tethered rhodium photo-oxidant strategically placed to probe charge transport. RESULTS: DX assemblies support long-range charge transport selectively down the base stack bearing the intercalated photo-oxidant. Despite tight packing, no electron transfer (ET) crossover to the adjacent base stack is observed. Moreover, the base stack of a DX assembly is well-coupled and less susceptible than duplex DNA to stacking perturbations. Introducing a double mismatch along the path for charge transport entirely disrupts long-range ET in duplex DNA, but only marginally decreases it in the analogous stack within DX molecules. CONCLUSIONS: The path for charge transport in a DX DNA assembly is determined directly by base stacking. As a result, the two closely packed stacks within this assembly are electronically insulated from one another. Therefore, DX DNA assemblies may serve as robust, insulated conduits for charge transport in nanoscale devices.