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7 macrophages, and significantly reduced bacterial load in the lungs of infected mice. Flow cytometric and time lapse fluorescence microscopy indicate mycobacterial membrane damage as the likely mechanism of action. These data demonstrate that peptoids are a novel class of antimicrobial which warrant further investigation and development as therapeutics against TB. Copyright © 2020 Khara, Mojsoska, Mukherjee, Langford, Robertson, Jenssen, Ee and Newton.Both CO and H2 can be utilized as energy sources during the autotrophic growth of Clostridium ljungdahlii. In principle, CO is a more energetically and thermodynamically favorable energy source for gas fermentation in comparison to H2. Therefore, metabolism may vary during growth under different energy sources. In this study, C. ljungdahlii was fed with CO and/or CO2/H2 at pH 6.0 with a gas pressure of 0.1 MPa. C. ljungdahlii primarily produced acetate in the presence of H2 as an energy source, but produced alcohols with CO as an energy source under the same fermentation conditions. A key enzyme activity assay, metabolic flux analysis, and comparative transcriptomics were performed for investigating the response mechanism of C. ljungdahlii under different energy sources. A CO dehydrogenase and an aldehydeferredoxin oxidoreductase were found to play important roles in CO utilization and alcohol production. Based on these findings, novel metabolic schemes are proposed for C. ljungdahlii growing on CO and/or CO2/H2. These schemes indicate that more ATP is produced during CO-fermentation than during H2-fermentation, leading to increased alcohol production. Copyright © 2020 Zhu, Liu, Zhou, Yi, Lun, Wang, Tang and Li.The spread of multidrug antibiotic resistance (MDR) is a widely recognized crisis in the treatment of bacterial infections, including those occurring in military communities. Recently, the World Health Organization published its first ever list of antibiotic-resistant "priority pathogens" - a catalog of 12 families of bacteria that pose the greatest threat to human health with A. baumannii listed in the "Priority 1 Critical" category of pathogens. With the increasing prevalence of antibiotic resistance and limited development of new classes of antibiotics, alternative antimicrobial therapies are needed, with lytic bacteriophage (phage) specifically targeted against each of the high priority bacterial infections as a potential approach currently in development toward regulatory approval for clinical use. Balb/c mice were prophylactically administered PBS or phage selected against A. baumannii strain AB5075. After 3 weeks, mice were anesthetized, wounded (dorsal), and challenged topically with AB5075. Following target. In regards to their therapeutic efficacy, administration of phage treatment effectively decreased wound size of mice infected with AB5075 without adverse effects. In conclusion, our data demonstrate that phage can serve as a safe and effective novel therapeutic agent against A. MEDICA16 concentration baumannii without adverse reactions to the host and pre-exposure to phage does not seem to adversely affect therapeutic efficacy. This study is an important proof of concept to support the efforts to develop phage as a novel therapeutic product for treatment of complex bacterial wound infections. Copyright © 2020 Rouse, Stanbro, Roman, Lipinski, Jacobs, Biswas, Regeimbal, Henry, Stockelman and Simons.Two-component signal transduction systems are still poorly functionally characterized in the model cyanobacterium Synechocystis sp. PCC 6803. To address the issue, a GC-MS based comparative metabolomic analysis was conducted on a library of 44 knockout mutants for the response regulators (RRs) in Synechocystis. The metabolomic profiling analysis showed that 7 RRs mutants, namely Δslr1909, Δsll1291, Δslr6040, Δsll1330, Δslr2024, Δslr1584, and Δslr1693, were significantly different at metabolomic level, although their growth patterns are similar to the wild type under the normal autotrophic growth condition, suggesting regulatory diversity of RRs at metabolite level in Synechocystis. Additionally, a detailed metabolomic analysis coupled with RT-PCR verification led to useful clues for possible function of these 7 RRs, which were found involved in regulation of multiple aspects of cellular metabolisms in Synechocystis. Moreover, an integrative metabolomic and evolutionary analysis of all RR showed that four groups of RR genes clustered together in both metabolomic and evolutionary trees, suggesting of possible functional conservation of these RRs during the evolutionary process. Meanwhile, six groups of RRs with close evolutionary origin were found with different metabolomic profiles, suggesting possible functional changes during evolution. In contrast, more than 10 groups of RR genes with different clustering patterns in the evolutionary tree were found clustered together in metabolomics-based tree, suggesting possible functional convergences during the evolution. This study provided a metabolomic view of RR function, and the most needed functional clues for further characterization of these regulatory proteins in Synechocystis. Copyright © 2020 Shi, Chen and Zhang.The human immune response that controls Plasmodium infection in the liver and blood stages of the parasite life cycle is composed by both pro- and anti-inflammatory programs. Pro-inflammatory responses primarily mediated by IFN-γ controls the infection, but also induce tolerogenic mechanisms to limit host damage, including the tryptophan (TRP) catabolism pathway mediated by the enzyme Indoleamine 2,3-Dioxygenase (IDO1), an enzyme that catalyzes the degradation of TRP to kynurenines (KYN). Here we assessed total serum kynurenines and cytokine dynamics in a cohort of natural Plasmodium vivax human infection and compared them to those of endemic healthy controls and other febrile diseases. In acute malaria, the absolute free kynurenine (KYN) serum levels and the KYN to TRP (KYN/TRP) ratio were significantly elevated in patients compared to healthy controls. Individuals with a diagnosis of a first malaria episode had higher serum KYN levels than individuals with a previous malaria episode. We observed an inverse relationship between the serum levels of IFN-γ and IL-10 in patients with a first malaria episode compared to those of subjects with previous history of malaria.
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