A team from the UK, Germany, and Finland explores host-microbe metabolic interactions that may influence response to cancer therapies such as treatment with fluoropyrimidine colorectal cancer drugs. In the worm model organism Caenorhabditis elegans, the researchers used three-way genetic screens with worms fed various Escherichia coli strains and different bacterial species — along with liquid chromatography and mass spectrometry — to assess host-microbe interactions and metabolic processes in the gut microbiome that might impact fluoropyrimidine response. Their results suggest microbes in the host gut may boost or dial down fluoropyrimidine response in C. elegans.
In a related study, researchers from the University of Massachusetts and Northwestern University report on a role for bacterial metabolism in response to three chemotherapeutic drugs in C. elegans. After screening C. elegans phenotypes after exposure to 11 drugs, the team narrowed in on three chemotherapy drugs for further study: 5-fluorouracil, 5-fluoro-2'-deoxyuridine, and camptothecin. Results from screens done with these drugs, in combaination with one of bacterial species in C. elegans, hint that some bacteria can bolster response to some drugs but diminish the effects of others. The authors note that microbe metabolism may also impact the toxicity or potential side effects that such drugs have in the host.
Researchers from the Netherlands and Israel report on ties between transcription rate, messenger RNA translation, and N6-adenosine methylation — identified using a reporter gene screen for human promoter activity, CRISPR-Case9-based genetic editing, and in vitro experiments. The results of these and other experiments suggest "genes possessing strong transcriptional activity give rise to mRNAs with greater capacity to produce proteins," the authors say. "We propose that this link is mediated, at least in part, by the co-transcriptional N6-methylation of adenosines in mRNA — the m6A modification."