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Repeated Exposure Enhanced Toxicity of Clarithromycin on Microcystis aeruginosa versus Single Exposure through Photosynthesis, Oxidative Stress and Energy Metabolism shift

ABSTRACT: Antibiotics are increasingly detected in aquatic environments, and their potential ecological risk is a concern. However, most antibiotic toxicity studies were performed with single exposure experiments. Here, we studied the effects and mechanisms of repeated clarithromycin (CLA) exposure on the algae Microcystis aeruginosa compared to the results of a single exposure. The 96-h effective concentration of CLA was 13.37 μg/L upon single exposure but was reduced to 6.90 μg/L upon repeated exposure. Single-exposure CLA inhibited algal photosynthesis by disrupting energy absorption, dissipation and trapping, reaction center activation, and electron transport, thereby inducing oxidative stress and ultrastructural damage. CLA also upregulated glycolysis, pyruvate metabolism, and the tricarboxylic acid cycle. Stronger inhibition of algal growth was observed under repeated exposure via effects on photosynthetic pigments, biosynthesis of reaction center subunits, and electron transport, inducing more substantial oxidative damage. Furthermore, repeated exposure reduced carbohydrate utilization by blocking the pentose phosphate pathway, which changed the characteristics of extracellular polymeric substances and eventually impaired algal self-defense. Risk quotients calculated from repeated exposure were higher than 1, indicating significant ecological risks. This study elucidated the severe influence of repeated antibiotic exposure on algae, providing new insights into antibiotic risk assessment.

ORGANISM(S): Microcystis Aeruginosa G-01

SUBMITTER: Jiang Hu

PROVIDER: PXD046918 | iProX | Mon Nov 13 00:00:00 GMT 2023

REPOSITORIES: iProX

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Project description:Bronchial epithelial cells, which line the airway of the respiratory tract, undergo genome-wide level changes in gene expression and DNA methylation particularly when exposed to fine (< 2.5 µm) PM (PM2.5). Although some of these changes have been reported in other studies, a comparison of how different doses and duration of exposure affect both the gene transcriptome and DNA methylome has not been done. We exposed BEAS-2B, a bronchial epithelial cell line, to a single exposure of high (30 µg/cm2) or low (1 µg/cm2) dose of PM2.5 (obtained from Beijing, China in 2015) for 24 hours. We also exposed BEAS-2B cells to repeated exposures of low dose (1 µg/cm2) PM2.5 every day for seven days. We then examined the transcriptomic changes (by RNA-Seq) and DNA methylomic changes (by enhanced reduced representation bisulfite sequencing). Widespread changes in gene expression occurred after cells were exposed to a single, high dose (30 µg/cm2) exposure of PM2.5 for 24 h. These genes were enriched in pathways regulating MAPK signaling, PI3K-Akt signaling, cytokine interactions, IL6, and P53. DNA methylomic analysis showed that nearly half of the differentially expressed genes were found to also have DNA methylation changes. Cells exposed to a lower dose (1 µg/cm2) of PM2.5 demonstrated a similar, but more attenuated change in gene expression. Cells exposed to repeated doses of PM2.5 for seven days, however, demonstrated a different set of genes that were differentially expressed compared to a single exposure. The DNA methylation changes that occurred with repeated, low dose exposure were also different from single high dose exposures and skewed towards overall hypomethylation. This hypomethylation corresponded with an increase in expression of ten-eleven translocation enzymes. Overall, these data demonstrate how variations in dose and duration of PM2.5 exposure induce distinct differences in the transcriptomic and DNA methylomic profile of bronchial epithelial cells.

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Repeated Exposure Enhanced Toxicity of Clarithromycin on Microcystis aeruginosa versus Single Exposure through Photosynthesis, Oxidative Stress and Energy Metabolism shift

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