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Pearson, P.

Publications and source records attributed to Pearson, P..

2 recordsLinked to original sources
bioRxiv2024

Effects of Inosine-5'-Monophosphate Dehydrogenase (IMPDH/GuaB) Inhibitors on Borrelia burgdorferi Growth in Standard and Modified Culture Conditions

Borrelia burgdorferis Inosine-5-Monophosphate dehydrogenase (IMPDH, GuaB) is a potential therapeutic target. GuaB is not needed for B. burgdorferi survival and replication in standard growth media, therefore our ability to test novel drugs against the whole organism is limited to tests using mammalian hosts. Modifications to standard culture conditions that can induce borreliastatic effects of GuaB inhibitors will enhance our ability to evaluate these inhibitors. This study aimed to evaluate basic modifications to standard growth media that can achieve this objective. Effects of GuaB inhibitors (mycophenolic acid, 6-Chloropurine) were compared in standard Barbour-Stoenner-Kelly-II (BSK-II) medium with BSK-II modified to 60% concentration rabbit serum, using B. burgdorferi 5A1. Effects were also evaluated with another BSK-II modification with the direct supplementation of hypoxanthine, adenine, and nicotinamide (75 M each). In standard BSK-II, neither mycophenolic acid nor 6-Chloropurine riboside affected B. burgdorferi growth. An ANOVA showed significant, dose-dependent interactions between culture condition and treatment considering modified growth conditions (F = 4.471, P = 0.001). Mycophenolic acid at 250 M reduced replication by 48 and 50% (P < 0.001 each). 6-Chloropurine riboside was more effective in both conditions at 250 M, reducing growth by 64 and 65% (P < 0.001 each). Effects of GuaB inhibitors were shown against whole organism Borrelia burgdorferi for the first time. Modification of BSK-II medium with physiologically relevant levels of mammalian serum supports replication and induces GuaB inhibitor-mediated suppression of replication. Effects of 6-Chloropurine riboside were demonstrated for the first time, indicating that B. burgdorferi can salvage and phosphorylate these analogue purine derivatives. These molecules can be manipulated to better inhibit replication. Optimisation will allow the assessment of novel Borrelia-specific IMPDH inhibitor molecules in culture for Lyme disease interventions. HighlightsO_LIEffects of IMPDH inhibitors are shown against whole organism Borrelia burgdorferi for the first time. C_LIO_LIModification of BSK-II medium with physiologically relevant levels of mammalian serum supports replication and induces IMPDH inhibitor-mediated suppression of replication. C_LIO_LIEffects of 6-Chloropurine riboside are demonstrated for the first time, indicating that B. burgdorferi can salvage and phosphorylate these analogue purine derivatives. These molecules can be manipulated to better inhibit replication. C_LIO_LIOptimisation of modified BSK-II will allow the assessment of novel Borrelia-specific IMPDH inhibitor molecules in culture for Lyme disease interventions. C_LI

microbiology↗
bioRxiv2019

Heating quinoa shoots results in yield loss by inhibiting fruit production and delaying maturity

Increasing global temperatures and a growing world population create the need to develop crop varieties that yield more in warmer climates. There is growing interest in expanding quinoa cultivation, because of quinoas ability to produce nutritious grain in poor soils, with little water and at high salinity. However, the main limitation to expanding quinoa cultivation is quinoas susceptibility to temperatures above ~32{degrees}C. This study investigates the phenotypes, genes, and mechanisms that may affect quinoa seed yield at high temperatures. By using a differential heating system where only roots or only shoots were heated, quinoa yield losses were attributed to shoot heating. Plants with heated shoots lost 60% to 85% yield as compared to control. Yield losses were due to lower fruit production, which lowered the number of seeds produced per plant. Further, plants with heated shoots had delayed maturity and more non-reproductive shoot biomass, while plants with both heated roots and heated shoots produced more yield from panicles that escaped heat than control. This suggests that quinoa uses a type of avoidance strategy to survive heat. Gene expression analysis identified transcription factors differentially expressed in plants with heated shoots and low yield that had been previously associated with flower development and flower opening. Interestingly, in plants with heated shoots, flowers stayed closed during the day while control flowers were open. Although a closed flower may protect floral structures, this could also cause yield losses by limiting pollen dispersal, which is necessary to produce fruit in quinoas mostly female flowers.\n\nSignificance StatementThis study provides evidence that heating quinoa during flowering results in seed yield loss by lowering fruit production. Plants with low yield after heat treatment also matured more slowly, suggesting that quinoa may use a type of avoidance strategy to survive heat stress conditions. Genes differentially expressed under heat include genes involved in flower development and flower opening.

plant biology↗