Genomic perspective on the bacillus causing paratyphoid B fever.

Paratyphoid B fever (PTB) is caused by an invasive lineage (phylogroup 1, PG1) of Salmonella enterica serotype Paratyphi B (SPB). However, little was known about the global population structure, geographic distribution, and evolution of this pathogen. Here, we report a whole-genome analysis of 568 historical and contemporary SPB PG1 isolates, obtained globally, between 1898 and 2021.

Novel Dual-Target μ-Opioid Receptor and Dopamine D Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management.

The need for safer pain-management therapies with decreased abuse liability inspired a novel drug design that retains μ-opioid receptor (MOR)-mediated analgesia, while minimizing addictive liability. We recently demonstrated that targeting the dopamine D receptor (DR) with highly selective antagonists/partial agonists can reduce opioid self-administration and reinstatement to drug seeking in rodent models without diminishing antinociceptive effects. The identification of the DR as a target for the treatment of opioid use disorders prompted the idea of generating a class of ligands presenting bitopic or bivalent structures, allowing the dual-target binding of the MOR and DR.

Dependence of Biocatalysis on D/H Ratio: Possible Fundamental Differences for High-Level Biological Taxons.

The kinetics of biological reactions depends on the deuterium/protium (D/H) ratio in water. In this work, we describe the kinetic model of biocatalytic reactions in living organisms depending on the D/H ratio. We show that a change in the lifetime or other characteristics of the vital activity of some organisms in response to a decrease or increase in the content of deuterium in the environment can be a sign of a difference in taxons.

Synthesis of a deuterated 6-AmHap internal standard for the determination of hapten density in a heroin vaccine drug product.

A deuterated hapten was designed and synthesized that will be essential for a future study of residual hapten and stability of a hapten-protein conjugate. This hapten, 6-AmHap, was chosen for a heroin vaccine that is now slated for a Phase 1 clinical trial. A maleimide-thiol bioconjugation strategy was successfully applied to our heroin vaccine to connect the hapten 6-AmHap with an immunogenic carrier protein (tetanus toxoid, TT) through a trityl-protected 3-mercaptopropanamide linker.

Chemoenzymatic Total Synthesis of -Oxycodone: Second-, Third-, and Fourth-Generation Strategies.

Four distinct approaches to -oxycodone were designed and accomplished. All rely on the same starting material, the diene diol derived from phenethyl acetate by the whole-cell fermentation with JM109 (pDTG601A), a strain that overexpresses toluene dioxygenase. The key step in the first-generation approach involves the construction of the C-9/C-14 bond by a SmI-mediated cyclization of a keto aldehyde.

Tetrodotoxin: History, Biology, and Synthesis.

This review provides a comprehensive coverage of the history, biology and chemistry of tetrodotoxin (TTX). It traces the origin of this remarkable molecule all the way back to the ancient Chinese medicine records. The discovery of biological activity, isolation, and a brief overview of structure elucidation are summarized.

Global phylogeography and evolutionary history of Shigella dysenteriae type 1.

Together with plague, smallpox and typhus, epidemics of dysentery have been a major scourge of human populations for centuries(1). A previous genomic study concluded that Shigella dysenteriae type 1 (Sd1), the epidemic dysentery bacillus, emerged and spread worldwide after the First World War, with no clear pattern of transmission(2). This is not consistent with the massive cyclic dysentery epidemics reported in Europe during the eighteenth and nineteenth centuries(1,3,4) and the first isolation of Sd1 in Japan in 1897(5).

Differences in extended-spectrum beta-lactamase producing Escherichia coli virulence factor genes in the Baltic Sea region.

The aim of this study was to compare the prevalence of different virulence factor (VF) genes in extended-spectrum beta-lactamase (ESBL) producing Escherichia coli strains isolated from the Baltic Sea region. A total of 432 strains of phenotypically ESBL positive E. coli were collected from 20 institutions located in Estonia, Latvia, Lithuania, and the region of St.