Potential selection and maintenance of manure-originated multi-drug resistant plasmids at sub-clinical concentrations for tetracycline family antibiotics.

The goal of this study was to (a) determine the minimum selection concentrations of tetracycline family antibiotics necessary to maintain plasmids carrying tetracycline-resistant genes and (b) correlate these results to environmental hotspot concentrations reported in previous studies. This study used two plasmids (pT295A and pT413A) originating from dairy manure in a surrogate Escherichia coli host CV601. The minimum selection concentrations of antibiotics tested in nutrient-rich medium were determined as follows: 0.1 mg/L for oxytetracycline, 0.45 mg/L for chlortetracycline, and 0.13-0.25 mg/L for tetracycline. Mixing oxytetracycline and chlortetracycline had minimum selection concentration values increased 2-fold compared to those in single antibiotic tests. Minimum selection concentrations found in this study were lower than reported environmental hotspot concentrations, suggesting that tetracycline family antibiotics were likely to be the driver for the selection and maintenance of these plasmids. Relatively high plasmid loss rates (>90%) were observed when culturing a strain carrying a tetracycline-resistant plasmid in antibiotic-free nutrient-rich and nutrient-defined media. Overall, results suggested that these plasmids can be maintained at concentrations environmentally relevant in wastewater treatment plants, sewage, manure, and manured soil; however, they are unstable and easily lost in the absence of antibiotics.

Insights into high-grade serous carcinoma pathobiology using three-dimensional culture model systems.

Epithelial ovarian cancer (EOC) research has become more complex as researchers try to fully understand the metastatic process. Especially as we delve into the concept of tumour dormancy, where cells transition between proliferative and dormant states to survive during disease progression. Thus, the in vitro models used to conduct this research need to reflect this vast biological complexity. The innovation behind the many three-dimensional (3D) spheroid models has been refined to easily generate reproducible spheroids so that we may understand the various molecular signaling changes of cells during metastasis and determine therapeutic efficacy of treatments. This ingenuity was then used to develop the 3D ex vivo patient-derived organoid model, as well as multiple co-culture model systems for EOC research. Although, researchers need to continue to push the boundaries of these current models for in vitro and even in vivo work in the future. In this review, we describe the 3D models already in use, where these models can be developed further and how we can use these models to gain the most knowledge on EOC pathogenesis and discover new targeted therapies.