E. coli is the leading cause of bloodstream infections, yet scientists do not know which specific genes the bacterium switches on to invade the blood and trigger sepsis. Sepsis strikes around 50 million people each year, killing one in five. Bloodstream infections also drove one third of the 1.27 million deaths from antimicrobial resistance in 2019. The World Health Organization has ranked *E. coli* a critical priority for new treatments. Yet only about 40 antibiotics are in development, and many will not work against this type of bacterium. Without new approaches, annual deaths from resistant infections could reach 10 million by 2050. This project is fundamental science. It will systematically identify the genes and molecular machinery *E. coli* requires to cause bloodstream infection. The goal is not to test a drug, but to create a detailed molecular blueprint of how the pathogen operates inside the human body. If successful, this knowledge could reveal specific bacterial processes that future vaccines or inhibitors might block. That would give drug developers concrete targets to aim at, rather than searching in the dark. Similar fundamental work on bacterial genetics has previously underpinned the development of effective vaccines and narrow-spectrum antibiotics.
View original technical description
Escherichia coli is the bacterial pathogen most often associated with bloodstream infection. This is a major health concern considering that a patient acquiring such an infection can develop sepsis, the body's potentially lethal chain reaction to infection of the bloodstream. Sepsis affects around 50 million people worldwide every year, with a frightening one in five chance of death. Furthermore, bloodstream infections were responsible for one third of the 1.27 million deaths directly caused by antimicrobial resistance in 2019. The World Health Organization ranks E. coli as a critical priority for discovery of new treatment strategies, due to it being the leading organism responsible for deaths arising from drug resistance. There are currently around 40 new antibiotics in development. However, many of these are not active against Gram-negative bacteria such as E. coli and it is inevitable that they will not all win approval for clinical use. It is therefore clear that these potential drugs will not meet the increasing demand in society and, without the discovery of new treatment approaches, annual deaths from antimicrobial resistant infections are estimated to rise to 10 million by 2050. One strategy to combat this problem is to design targeted treatments against pathogens. However, in order to identify what these targets are, we must first gain a deep, fundamental understanding of how bacteria cause infection. Bacterial genes act as blueprints describing the molecular machinery that they use to live. However, pathogens can alter which genes they require in unique ways, making their blueprints difficult to understand depending on the type of infection. We currently lack an understanding of how E. coli uses its molecular machinery to infect the bloodstream and spread throughout the body. I will address this gap by discovering the specific genes and associated molecular processes that are required for E. coli to cause potentially lethal bloodstream infections. By understanding the molecular requirements of pathogens to function within the host, we can exploit this knowledge to develop vaccines or inhibitors that specifically block these processes. This research will reveal the underlying processes of bloodstream infection and therefore has the potential to reveal urgently needed targets for future drug development.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know