Scientists disable infectious bacteria by removing protein
Scientists at the John Innes Centre and the University of East Anglia have made an exciting discovery that could provide a new way to prevent bacterial infections in both humans and plants without triggering multi-drug resistance in bacteria.
When bacteria infect either a plant or a human they first have to move across the surface to a likely site of infection. Without this migration, the bacteria find it difficult to get inside the host and are far less able to cause infection.
The research team, led by Dr Jacob Malone from the JIC and UEA’s School of Biological Sciences, was curious about why there were high levels of a particular protein in bacteria when they came into contact with plants. Upon investigating this protein further they discovered it is an important, high-level controller of bacterial movement during plant and human infection. This protein could become a new target against which to develop anti-infective drugs and because the bacteria aren’t killed outright, also reduces the likelihood of the bacteria evolving to develop resistance to the drugs.
Dr Malone and his team study a type of bacteria called Pseudomonas, of which there are dozens of different species, including the pathogen P. aeruginosa, which causes around 7% of hospital acquired infections in the UK and is a major cause of mortality in cystic fibrosis patients. Understanding these bacteria is medically very important.
They have found that the ability of Pseudomonas to cause infection is compromised at an early stage when one key protein is removed from the bacterium.
The key protein is called RimK, and is present in hundreds of species of bacteria, including several important human pathogens, but its biological function has remained largely unknown.
Dr Malone’s team discovered a completely new function for RimK. When they removed it from bacteria, those bacteria weren’t able to move properly, which in turn affected their ability to initiate infections. When scientists examined the effect of RimK deletion on plants they found that spraying a plant with RimK deleted bacteria resulted in milder disease symptoms compared to when wild type bacteria was sprayed on the plant. However, if the early stages of infection were bypassed, for example, by injecting or forcing the bacteria into plant tissue, the RimK mutant bacteria were able to infect normally. This suggests that RimK is important during the early stages of (plant) infection only. Similar results were seen for both plant and human pathogenic Pseudomonas, suggesting a common mechanism for RimK activity in both types of bacteria.
In their paper published in PLoS Genetics, Dr Malone’s team showed that RimK works to control the way that many other proteins are made within bacteria. The research suggests that when a bacterium senses that it is in a new place to grow, such as on a plant leaf or on a human cell, it adapts to that environment by changing the production of hundreds of proteins. The RimK protein controls this change, making sure that the bacteria are able to move around and thrive in their new environment. When bacteria are modified in the laboratory so they don’t contain a RimK protein, this process doesn’t work properly and the bacteria are out of sync with their surroundings, meaning they don’t migrate when they should.
Dr Malone said: “We have found a completely new way in which bacteria control their responses to the environment: by modifying their production of proteins. This affects how a bacteria that grows on humans and plants can infect its host – if you disrupt that process, they find it difficult to start an infection.”
Dr Malone’s team hope that their insight into how the RimK-regulatory process works will influence future medical and plant research, by targeting this protein to help prevent both human and plant diseases.
Dr Malone said: “This information will be extremely useful for researchers working on plant and human diseases. Many people will have heard about the emergence of multidrug resistant bacteria – if we can target a protein that specifically controls infection rather than killing the bacteria outright, the bacteria are less likely to evolve and become resistant. This finding could give scientists a new target against which to develop anti-infective drugs.”
The John Innes Centre receives strategic funding from the Biological and Biotechnology Research Council (BBSRC). This work was funded by both a UK government grant from BBSRC and by the University of East Anglia.
Notes to editors
Dr Malone’s paper ‘Adaptive remodelling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation’ is published in PLoS Genetics.
About John Innes Centre
Our mission is to generate knowledge of plants and microbes through innovative research, to train scientists for the future, to apply our knowledge of nature’s diversity to benefit agriculture, the environment, human health and wellbeing, and engage with policy makers and the public.
To achieve these goals we establish pioneering long-term research objectives in plant and microbial science, with a focus on genetics. These objectives include promoting the translation of research through partnerships to develop improved crops and to make new products from microbes and plants for human health and other applications. We also create new approaches, technologies and resources that enable research advances and help industry to make new products. The knowledge, resources and trained researchers we generate help global societies address important challenges including providing sufficient and affordable food, making new products for human health and industrial applications, and developing sustainable bio-based manufacturing.
This provides a fertile environment for training the next generation of plant and microbial scientists, many of whom go on to careers in industry and academia, around the world.
The John Innes Centre is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC). In 2014-2015 the John Innes Centre received a total of £36.9M from BBSRC.
The University of East Anglia (UEA) is a UK top 15 university and ranks in the top 1% of universities in the world. Known for its world-leading research and outstanding student experience, it has achieved a Top 10 rating in the National Student Survey every year since the survey began. UEA is a leading member of the Norwich Research Park – one of Europe’s biggest concentrations of researchers in the fields of environment, health and plant science. www.uea.ac.uk.