Antibiotic resistance alters the ability of to invade bacteria from the respiratory microbiome.

The emergence and spread of antibiotic resistance in bacterial pathogens is a global health threat. One important unanswered question is how antibiotic resistance influences the ability of a pathogen to invade the host-associated microbiome. Here we investigate how antibiotic resistance impacts the ability of a bacterial pathogen to invade bacteria from the microbiome, using the opportunistic bacterial pathogen and the respiratory microbiome as our model system.

Regulatory fine-tuning of mcr-1 increases bacterial fitness and stabilises antibiotic resistance in agricultural settings.

Antibiotic resistance tends to carry fitness costs, making it difficult to understand how resistance can be maintained in the absence of continual antibiotic exposure. Here we investigate this problem in the context of mcr-1, a globally disseminated gene that confers resistance to colistin, an agricultural antibiotic that is used as a last resort for the treatment of multi-drug resistant infections. Here we show that regulatory evolution has fine-tuned the expression of mcr-1, allowing E.

High-throughput functional variant screens via in vivo production of single-stranded DNA.

Creating and characterizing individual genetic variants remains limited in scale, compared to the tremendous variation both existing in nature and envisioned by genome engineers. Here we introduce retron library recombineering (RLR), a methodology for high-throughput functional screens that surpasses the scale and specificity of CRISPR-Cas methods. We use the targeted reverse-transcription activity of retrons to produce single-stranded DNA (ssDNA) in vivo, incorporating edits at >90% efficiency and enabling multiplexed applications.

Circulating CD14 HLA-DR monocytic cells as a biomarker for epithelial ovarian cancer progression.

Problem: Previous studies identified circulating CD14 HLA-DR monocytic cells as an immune suppressive subset in solid malignancies, such as prostate, renal cell carcinoma, and pancreatic cancer. Such monocytic cells have been implicated not only in tumour progression but also as a potential barrier for immunotherapy. This study examined the relationship between the frequency of circulating monocytic cells and epithelial ovarian cancer (EOC) progression pre- and post-frontline chemotherapy, defined by disease stage, which is a leading prognostic factor for this malignancy.

Engineering Isoprenoid Quinone Production in Yeast.

Isoprenoid quinones are bioactive molecules that include an isoprenoid chain and a quinone head. They are traditionally found to be involved in primary metabolism, where they act as electron transporters, but specialized isoprenoid quinones are also produced by all domains of life. Here, we report the engineering of a baker's yeast strain, EPYFA3, for the production of isoprenoid quinones.