Peptide-to-Small Molecule: Discovery of Non-Covalent, Active-Site Inhibitors of β-Herpesvirus Proteases.

Viral proteases, the key enzymes that regulate viral replication and assembly, are promising targets for antiviral drug discovery. Herpesvirus proteases are enzymes with no crystallographically confirmed noncovalent active-site binders, owing to their shallow and polar substrate-binding pockets. Here, we applied our previously reported "Peptide-to-Small Molecule" strategy to generate novel inhibitors of β-herpesvirus proteases.

Immune response and protective efficacy of the SARS-CoV-2 recombinant spike protein vaccine S-268019-b in mice.

Vaccines that efficiently target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for coronavirus disease (COVID-19), are the best means for controlling viral spread. This study evaluated the efficacy of the COVID-19 vaccine S-268019-b, which comprises the recombinant full-length SARS-CoV-2 spike protein S-910823 (antigen) and A-910823 (adjuvant). In addition to eliciting both Th1-type and Th2-type cellular immune responses, two doses of S-910823 plus A-910823 induced anti-spike protein IgG antibodies and neutralizing antibodies against SARS-CoV-2.

The crystal structure of multidrug-resistance regulator RamR with multiple drugs.

RamR is a transcriptional repressor of the gene-encoding RamA protein, which controls the expression of the multidrug efflux system genes acrAB-tolC. RamR is an important multidrug-resistance factor, however, its structure and the identity of the molecules to which it responds have been unknown. Here, we report the crystal structure of RamR in complex with multiple drugs, including berberine, crystal violet, dequalinium, ethidium bromide and rhodamine 6G.

Effects of indole on drug resistance and virulence of Salmonella enterica serovar Typhimurium revealed by genome-wide analyses.

Background: Many Gram-positive and Gram-negative bacteria produce large quantities of indole as an intercellular signal in microbial communities. Indole demonstrated to affect gene expression in Escherichia coli as an intra-species signaling molecule. In contrast to E.

Regulation of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium in response to indole and paraquat.

Salmonella enterica serovar Typhimurium has at least nine multidrug efflux pumps. Among these, AcrAB is constitutively expressed and is the most efficient, playing a role in both drug resistance and virulence. The acrAB locus is induced by indole, Escherichia coli-conditioned medium, and bile salts.

Roles of Salmonella multidrug efflux pumps in tigecycline resistance.

Objectives: salmonella enterica strains exhibiting decreased susceptibility to tigecycline have been reported. In this study, we sought to elucidate the roles of Salmonella multidrug efflux pumps and AcrAB regulators in tigecycline resistance.

Methods: we examined the involvement of multidrug efflux pumps and AcrAB regulators in resistance to tigecycline and other glycylcyclines by determining the MICs of the drugs for Salmonella multidrug efflux pump and AcrAB regulator-overproducing or -deleted strains.

Regulation and physiological function of multidrug efflux pumps in Escherichia coli and Salmonella.

Multidrug efflux is an obstacle to the successful treatment of infectious diseases, and it is mediated by multidrug efflux pumps that recognize and export a broad spectrum of chemically dissimilar toxic compounds. Many bacterial genome sequences have been determined, allowing us to identify drug efflux genes encoded in the bacterial genome. Here, we present an approach to identifying drug efflux genes and their regulatory networks in Escherichia coli and Salmonella.

AcrAB multidrug efflux pump regulation in Salmonella enterica serovar Typhimurium by RamA in response to environmental signals.

Salmonella enterica serovar Typhimurium has at least nine multidrug efflux pumps. Among these pumps, AcrAB is effective in generating drug resistance and has wide substrate specificity. Here we report that indole, bile, and an Escherichia coli conditioned medium induced the AcrAB pump in Salmonella through a specific regulator, RamA.

Regulation of multidrug efflux systems involved in multidrug and metal resistance of Salmonella enterica serovar Typhimurium.

Multidrug-resistant strains of Salmonella are now encountered frequently, and the rates of multidrug resistance have increased considerably in recent years. Here, we report that the two-component regulatory system BaeSR increases multidrug and metal resistance in Salmonella through the induction of drug efflux systems. Screening of random fragments of genomic DNA for the ability to increase beta-lactam resistance in Salmonella enterica led to the isolation of a plasmid containing baeR, which codes for the response regulator of BaeSR.