MORF reveals new biology in a foodborne pathogen

How do pathogenic bacteria sometimes gain a foothold in the human body? Why do the same bacteria sometimes cause infections, and sometimes remain harmless? These are questions of vital importance for modern medicine, especially as antibiotic resistance is making it harder to combat infections that do occur. In the foodborne pathogen E. coli, one key molecule is d-Serine, a metabolite that is toxic to the bacterium, and typically prevents its growth in most body tissues. However, d-Serine is virtually absent from the intestines, explaining why some E. coli strains can cause severe gastro-intestinal illness.

The Role of d-Serine in E. coli Infection

Understanding how and why d-Serine causes growth arrest in E. coli was the key question that James Connolly, Nicky O’Boyle and co-workers set out to address in a 2021 study published in Microbiology. The authors looked at the response to d-Serine in E. coli strains that are known to colonise three different sites in the human body using transcriptomics, and discovered intriguing changes in gene expression in response to d-Serine. Back in 2021, the MORF team thought this study would make a perfect showcase for our visualisation tools, and collaborated with the authors to make the data accessible in MORF. But what we did not anticipate was just how using MORF would change the authors’ interpretation of their data, and help deliver new and follow-on publications.

A Transcriptomics Study Reveals Clues

While re-analysing the data with MORF’s transcriptomics tools, the authors found that a previously unannotated small RNA, stood out as the most significantly upregulated transcript. Now, in a new study from the O’Boyle group, led by Ella Rellis, the authors demonstrate the potential role of this transcript in the response to d-Serine. With MORF’s advanced sequence annotations, the nature of the small RNA became clear; it was SgrS, a regulatory RNA normally involved in the response to accumulation of toxic levels of glucose-6-phosphate or similar sugar/phosphate conjugates. The potential role of SgrS in the response to d-Serine was completely unexpected, and suggests that the growth arrest in E.coli is caused at least in part by the impact of d-Serine on sugar metabolism. The authors demonstrate that SgrS is not involved in causing growth arrest, but rather acts to help the bacteria to mitigate the metabolic stress caused by d-Serine, providing exciting new research avenues to help understand pathogenic niche determination in bacteria.

MORF Re-analysis Uncovers an Unexpected RNA Regulator

The MORF team are delighted to see such important insights being delivered by our unique bioinformatic tools. “This is exactly why we built MORF–” says Professor Gavin Thomas, Chief Scientific Officer of MORF. “–To empower the research community to make new discoveries from their data, and to help get the best value out of datasets that are often expensively assembled, but only analysed in limited depth”. And with new tools such as MORF Genomes now available, the study by Rellis and O’Boyle represents only the first of many such discoveries that will be enabled by MORF.