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Batarseh, S. N.

Publications and source records attributed to Batarseh, S. N..

2 recordsLinked to original sources

Phenotypic and genotypic adaptation of E. coli to thermal stress is contingent on genetic background

Evolution can be contingent on history, but we do not yet have a clear understanding of the processes and dynamics that govern contingency. Here we performed the second phase of a two-phase evolution experiment to investigate features of contingency. The first phase of the experiment was based on Escherichia coli clones that had evolved population at the stressful temperature of 42.2{degrees}C. The Phase 1 lines generally evolved through two adaptive pathways: mutations of rpoB, which encodes the beta subunit of RNA polymerase, or through rho, a transcriptional terminator. We hypothesized that epistatic interactions within the two pathways constrained their future adaptative potential, thus affecting patterns of historical contingency. Using 10 different E. coli Founders representing both adaptive pathways, we performed a second phase of evolution at 19.0{degrees}C to investigate how prior genetic divergence or adaptive history (rpoB vs. rho) may affect the likelihood of parallel responses and evolutionary outcomes. We found that phenotype, as measured by relative fitness, was contingent on founder genotypes and pathways. This finding extended to genotypes, because E. coli from different Phase 1 histories evolved by adaptive mutations in distinct sets of genes. Our results suggest that evolution depends critically on genetic history, likely due to idiosyncratic epistatic interactions within and between evolutionary modules.

evolutionary biology↗

Unique role for caspase-8 in the release of IL-1β and active caspase-1 from viable human monocytes during Toxoplasma gondii infection

Monocytes are among the first cells recruited to sites of infection and major producers of the potent proinflammatory cytokine IL-1{beta}. We previously showed that IL-1{beta} release during Toxoplasma gondii infection of primary human monocytes requires the NLRP3 inflammasome and caspase-1 activity but is independent of gasdermin D and pyroptosis. To investigate potential mechanisms of pyroptosis-independent release of IL-1{beta} during T. gondii infection, we constructed caspases-1, -4, -5, or -8 knockout THP-1 monocytic cells. Genetic ablation of caspase-1 or -8, but not caspase-4 or -5, decreased IL-1{beta} release during T. gondii infection without affecting cell death. In contrast, TNF- and IL-6 secretion were unperturbed in caspase-8 knockout cells during T. gondii infection. Dual pharmacological inhibition of caspase-8 and RIPK1 in primary monocytes also decreased IL-1{beta} release without affecting cell viability or parasite infection efficiency. In addition, caspase-8 was required for the release of active caspase-1 from T. gondii-infected cells and for IL-1{beta} release during infection with the related apicomplexan parasite Neospora caninum. Surprisingly, caspase-8 was dispensable for the synthesis and cleavage of IL-1{beta}, but caspase-8 deficiency resulted in the retention of mature IL-1{beta} within cells. Our data indicate that during T. gondii infection of human monocytes, caspase-8 functions in a novel gasdermin D-independent mechanism controlling IL-1{beta} release from viable cells. This study expands on the known molecular pathways that promote IL-1{beta} in human immune cells and provides the first evidence of a role for caspase-8 in the mechanism of IL-1{beta} release during host defense against infection.

immunology↗