Scientists solve mystery of how predatory bacteria recognizes prey
A decades-old mystery of how natural antimicrobial predatory bacteria are able to recognize and kill other bacteria may have been solved, according to new research.
In a study published today (4th January) in Nature Microbiology, researchers from the University of Birmingham and the University of Nottingham have discovered how natural antimicrobial predatory bacteria, called Bdellovibrio bacterivorous, produce fibre-like proteins on their surface to ensnare prey.
This discovery may enable scientists to use these predators to target and kill problematic bacteria that cause issues in healthcare, food spoilage and the environment.
The research was funded by the Wellcome Trust Investigator in Science Award (209437/Z/17/Z).
Professor of Structural Biology at the University of Birmingham, Andrew Lovering said: “Since the 1960s Bdellovibrio bacterivorous has been known to hunt and kill other bacteria by entering the target cells and eating them from the inside before later bursting out. The question that had stumped scientists was ‘how do these cells make a firm attachment when we know how varied their bacterial targets are?’”
Professor Lovering and Professor Liz Sockett, from the School of Life Sciences at the University of Nottingham, have been collaborating in this field for almost 15 years. The breakthrough came when Sam Greenwood an undergraduate student, and Asmaa Al-Bayati, a PhD student in the Sockett lab, discovered that the Bdellovibrio predators lay down a sturdy vesicle (a “pinched-off” part of the predator cell envelope) when invading their prey.
Professor Liz Sockett explained: “The vesicle creates a kind of airlock or keyhole allowing Bdellovibrio entry into the prey cell. We were then able to isolate this vesicle from the dead prey, which is a first in this field. The vesicle was analysed to reveal the tools used during the preceding event of predator/prey contact. We thought of it as a bit like a locksmith leaving the pick, or key, as evidence, in the keyhole.
“By looking at the vesicle contents, we discovered that because Bdellovibrio doesn’t know which bacteria it will meet, it deploys a range of similar prey recognition molecules on its surface, creating lots of different ‘keys’ to ‘unlock’ lots of different types of prey.”
The researchers then undertook an individual analysis of the molecules, demonstrating that they form long fibres, approximately ten times longer than common globular proteins. This allows them to operate at a distance and “feel” for prey in the vicinity.
In total, the labs counted 21 different fibres. Researchers Dr Simon Caulton, Dr Carey Lambert and Dr Jess Tyson worked on how they operated both at the cellular and molecular level. They were supported by fibre gene-engineering by Paul Radford and Rob Till. The team then began to attempt linking a particular fibre to a particular prey-surface molecule. Finding out which fibre matches which prey, could enable an engineering approach which sees bespoke predators targeting different types of bacteria.
Professor Lovering continued: “Because the predator strain we were looking at comes from the soil it has a wide killing range, making this identification of these fibre and prey pairs very difficult. However, on the fifth attempt to find the partners we discovered a chemical signature on the outside of prey bacteria that was a tight fit to the fibre tip. This is the first time a feature of Bdellovibrio has been matched to prey selection.”
Scientists in this field will now be able to use these discoveries to ask which fibre set is used by the different predators they study and potentially attribute these to specific prey. Improving understanding of these predator bacteria could enable their usage as antibiotics, to kill bacteria that degrade food, or ones which are harmful to the environment.
Professor Lovering concluded: “We know that these bacteria can be helpful, and by fully understanding how they operate and find their prey, it opens up a world of new discoveries and possibilities.”
ENDS
JOURNAL
Nature Microbiology
METHOD OF RESEARCH
Experimental study
SUBJECT OF RESEARCH
Not applicable
ARTICLE TITLE
Bdellovibrio bacteriovorus uses chimeric fibre proteins to recognize and invade a broad range of bacterial hosts
ARTICLE PUBLICATION DATE
4-Jan-2024
The surprisingly resourceful ways bacteria thrive in the human gut
Survey of bacterial genomes highlights the arsenal of enzymes microbes use to produce energy in the oxygen-poor environment of the gut
The gut microbiome is so useful to human digestion and health that it is often called an extra digestive organ. This vast collection of bacteria and other microorganisms in the intestine helps us break down foods and produce nutrients or other metabolites that impact human health in a myriad of ways. New research from the University of Chicago shows that some groups of these microbial helpers are amazingly resourceful too, with a large repertoire of genes that help them generate energy for themselves and potentially influence human health as well.
The paper, published January 4, 2024, in Nature Microbiology, identified 22 metabolites that three distantly related families of gut bacteria use as alternatives to oxygen for respiration in the anaerobic environment of the gut. These bacteria also have up to hundreds of copies of genes for producing the enzymes that process these alternate metabolites – many more than have been measured in bacteria that live outside the gut. These results suggest that anaerobic gut bacteria may have the ability to produce energy from hundreds of other compounds as well.
“These are examples of some of the peculiar metabolisms that act on all these different metabolites produced by the gut microbiome,” said Sam Light, PhD, Neubauer Family Assistant Professor of Microbiology at UChicago and senior author of the study. “This is interesting because one of the main ways the microbiome impacts our health is by making or modifying these small molecules that can then enter our bloodstream and act like drugs.”
At the organism level, we typically think of respiration as the process of breathing in oxygen. At the cellular level, respiration describes an energy-generating biochemical process. Most cells use oxygen for respiration, but in anaerobic environments like the inside of the intestine, cells have evolved to use other molecules.
Cells possess two main types of metabolism to produce energy: fermentation and respiration. In fermentation, the cell breaks down molecules to generate energy directly. Respiration involves two molecules: an electron donor and an electron acceptor. A classic example of this process uses glucose as a donor and oxygen as the acceptor. The cells break down the glucose by shuttling extracted electrons through a series of steps before their final transfer to an oxygen molecule. This prompts the cell to generate ATP, or adenosine triphosphate: the basic source of energy for use and storage at the cellular level.
Most of the microbes living in the gut use fermentation, but there are also several known types of bacteria with respiratory metabolisms, including those that use carbon dioxide and sulfate electron acceptors. For the new study, Light and his colleagues analyzed a database of more than 1,500 genomes from a database of human gut bacteria. They saw a surprising distribution of genes that produce reductases, which are enzymes that use different respiratory electron acceptors. While most of the genomes encode just a few reductases, a small subset encodes more than 30 different ones. These bacteria weren’t closely related; they came from three distinct and distantly related families (Burkholderiaceae, Eggerthellaceae, and Erysipelotrichaceae) separated by hundreds of millions of years of evolutionary history.
These bacteria appear to be more resourceful than bacteria with respiratory metabolisms that live outside of a host organism, which mostly use inorganic compounds. The respiratory gut bacteria Light and team identified specialize in various organic metabolites, which makes sense given the constant food supply.
"There is so much organic matter in the gut that comes from the food we eat. It’s chemically complex, and you need more enzymes to accommodate it in that environment,” Light said. “We think this variety of genes enables gut bacteria to use a lot of different things that come their way.”
Some of the metabolites they use also have interesting implications for human health in the gut. People with type 2 diabetes, for example, have higher levels of an amino acid byproduct called imidazole propionate in their blood. Another metabolite, resveratrol, impacts several metabolic and immune system processes, and itaconate is produced by macrophages in response to infections.
Light hopes that more research like this will help us understand the function of different microbes in the gut, which can in turn be leveraged to improve health.
“I'm hoping our understanding of these different metabolisms and how they work will enable us to come up with strategies to intervene – either through the diet or pharmacologically – to modulate the flow of metabolites through these various pathways,” he said. "So, in whatever context, like type 2 diabetes or following an infection, we could control which metabolites are being produced to have a therapeutic benefit.”
The study, “Dietary- and host-derived metabolites are used by diverse gut bacteria for anaerobic respiration,” was supported by funding from the National Institutes of Health (T32DK007074, 1S10OD020062-01, K22AI144031, and R35GM146969) and the Searle Scholars Program. Additional authors include Alexander S. Little, Isaac T. Younker, Matthew S. Schechter, Paola Nol Bernardino, Joshua Stemczynski, Kaylie Scorza, Michael W. Mullowney, Deepti Sharan, Emily Waligurski, Rita Smith, Ramanujam Ramanswamy, William Leiter, David Moran, Mary McMillin, Matthew A. Odenwald, Ashley M. Sidebottom, Anitha Sundararajan and Eric G. Pamer from the University of Chicago; Raphaël Méheust from Université d'Évry and Université Paris-Saclay, France; Anthony T. Iavarone from the University of California, Berkeley; and A. Murat Eren from the University of Oldenburg, Germany.
JOURNAL
Nature Microbiology
METHOD OF RESEARCH
Data/statistical analysis
SUBJECT OF RESEARCH
Cells
ARTICLE TITLE
Dietary- and host-derived metabolites are used by diverse gut bacteria for anaerobic respiration
ARTICLE PUBLICATION DATE
4-Jan-2024
