Redox Cycling Dioxonaphthoimidazoliums Disrupt Iron Homeostasis in Mycobacterium bovis Bacillus Calmette-Guérin.

The dioxonaphthoimidazolium scaffold is a novel, highly bactericidal redox cycling antituberculosis chemotype that is reliant on the respiratory enzyme Type II NADH dehydrogenase (NDH2) for the generation of reactive oxygen species (ROS). Here, we employed Mycobacterium bovis Bacillus Calmette-Guérin (M. bovis BCG) reporter strains to show that ROS generated by the redox cycler SA23 simulated an iron deficient state in the bacteria, which led to a compensatory increase in the expression of the iron acquisition gene while collaterally reducing the expression of the iron storage gene.

Selective Inhibition of Plasmodium falciparum ATPase 6 by Artemisinins and Identification of New Classes of Inhibitors after Expression in Yeast.

Treatment failures with artemisinin combination therapies (ACTs) threaten global efforts to eradicate malaria. They highlight the importance of identifying drug targets and new inhibitors and of studying how existing antimalarial classes work. Here, we report the successful development of a heterologous expression-based compound-screening tool.

Metabolic Responses of "Big Six" Escherichia coli in Wheat Flour to Thermal Treatment Revealed by Nuclear Magnetic Resonance Spectroscopy.

Escherichia coli outbreaks linked to wheat flour consumption have kept emerging in recent years, which necessitated an antimicrobial step being incorporated into the flour production process. The objectives of this study were to holistically evaluate the sanitizing efficacy of thermal treatment at 60 and 70°C against the "big six" E. coli strains (O26:H11, O45:H2, O103:H11, O111, O121:H19, and O145) in wheat flour and to assess the strain-specific metabolic responses using nuclear magnetic resonance (NMR) spectroscopy.

Differentiating Closely Affiliated Lineages by a Novel Genetic Marker Identified via Computational Pangenome Analysis.

As a group, the genus dehalogenates a wide range of organohalide pollutants, but the range of organohalide compounds that can be utilized for reductive dehalogenation differs among strains. lineages cannot be reliably disambiguated in mixed communities using typical phylogenetic markers, which often confounds bioremediation efforts. Here, we describe a computational approach to identify genetic markers with improved discriminatory resolution.

Effects of Increasing Concentrations of Rifampicin on Different Mycobacterium tuberculosis Lineages in a Whole-Blood Bactericidal Activity Assay.

High-dose rifampicin improved bactericidal activity and culture conversion in early-phase tuberculosis (TB) trials, done mainly in Africa. We performed a whole-blood bactericidal activity (WBA) study to determine whether the effects of high-dose rifampicin differ across globally relevant TB strains and whether effects are similar in dormant bacilli that will be required for enhancing cure. Whole blood from healthy volunteers was spiked with rifampicin (range, 0.

High-Throughput Mutagenesis and Cross-Complementation Experiments Reveal Substrate Preference and Critical Residues of the Capsule Transporters in .

MOP (Multidrug/Oligosaccharidyl-lipid/Polysaccharide) family transporters are found in almost all life forms. They are responsible for transporting lipid-linked precursors across the cell membrane to support the synthesis of various glycoconjugates. While significant progress has been made in elucidating their transport mechanism, how these transporters select their substrates remains unclear.

Novel Freshwater Cyanophages Provide New Insights into Evolutionary Relationships between Freshwater and Marine Cyanophages.

Cyanobacteria and cyanophages are present widely in both freshwater and marine environments. However, freshwater cyanophages remain unknown largely due to the small numbers of cyanophage isolates despite their ecological and environmental significance. In this study, we present the characterization of two novel lytic freshwater cyanophages isolated from a tropical inland lake in Singapore, namely, cyanopodovirus S-SRP01 and cyanomyovirus S-SRM01, infecting two different strains of spp.

A Novel Attenuated Enterovirus A71 Mutant with VP1-V238A,K244R Exhibits Reduced Efficiency of Cell Entry/Exit and Augmented Binding Affinity to Sulfated Glycans.

Enterovirus A71 (EV-A71) is one of the major etiological agents of hand, foot, and mouth disease (HFMD), and infection occasionally leads to fatal neurological complications in children. However, only inactivated whole-virus vaccines against EV-A71 are commercially available in Mainland China. Furthermore, the mechanisms underlying the infectivity and pathogenesis of EV-A71 remain to be better understood.

Identification of Reductive Dehalogenases That Mediate Complete Debromination of Penta- and Tetrabrominated Diphenyl Ethers in spp.

Polybrominated diphenyl ethers (PBDEs) are persistent, highly toxic, and widely distributed environmental pollutants. The microbial populations and functional reductive dehalogenases (RDases) responsible for PBDE debromination in anoxic systems remain poorly understood, which confounds bioremediation of PBDE-contaminated sites. Here, we report a PBDE-debrominating enrichment culture dominated by a previously undescribed Dehalococcoides mccartyi population.