Food fight: Bacteria’s biological warfare

You’re not just eating for one. You’re eating for trillions.

We like to think of ourselves as an individual, but the truth is we are never alone. We are a buzzing hive of bacteria and other microbes that make up our ‘microbiome’. They eke out a living in whatever niches they can find, our skin or parts of our digestive system; we are an ecosystem.

Like all ecosystems there is competition for resources, and some microbes don’t take it lying down, they fight. I’ve written before about Cholera’s spring loaded dagger, but microbes have many means at their disposal, some release enzymes to chew off important bits of their competitors, or poison them. But a few go a step further; they use biological warfare: unleashing viruses to kill off the competition.

Over millions of years of evolution with our microbial hoard we’ve come to rely on them; some help in digestion, breaking up long molecules into smaller chunks more manageable by our own cells, or by tutoring our immune system, helping it to learn what’s acceptable and what’s not. They’re an important, maybe even essential, part of normal, healthy life.

We’re only just starting to peek through the window of this world, to understand how it works and just how important our relationship with our microbiome is. But microbes, like bacteria and fungi, aren’t the whole picture; there’re other things hidden in there too, more subtle, less obvious.

Ever since we’ve been able to peer into, and ‘read’, the genomes of plants, animals and microbes we’ve seen traces of DNA from viruses littered throughout them. Even complete viral genomes can be found, often silenced somehow; but everything needed to make the fully functioning virus is there. They’re an important part of our own genomes; and make up around 8% of our total genetic inheritance.

Enterococcus faecalis

Enterococcus faecalis. Lovely looking isn’t it?

One bacterium, a denizen of the lower intestine, called Enterococcus faecalis has been found to harbour 7 ‘prophages’—viral genomes carried in circular strings of DNA—and it uses them as a weapon. A team from The University of Texas and Howard Hughes Medical Institute, led by Associate Professor Lora V. Hooper,  has revealed that this bacterium produces viruses (also called ‘bacteriophages’ or just ‘phages’ when they infect bacteria) that attack related species competing for the same resources.

But it doesn’t just chug out these proviruses randomly; it selects from them. It uses the structural components from prophage 1, providing a shell in which is carried a deadly payload. The payload comes from prophage 7 and contains the machinery needed to ‘lyse’, or split open, an infected bacterium.

At first the team couldn’t be sure that it was a combined virus like this that was the culprit. They had detected DNA for provirus 1 and 7, but only one virus particle. To check, they genetically engineered E. faecalis to make two new strains.

In one strain they removed prophage 1, the other, prophage 7. When they grew the strain without prophage 1, they saw no virus particles. Without prophage 7 they saw the virus particles, but they were non-functional. Only when both prophages 1 and 7 were present was the virus able to carry out its nefarious deeds.

To check if this really offers an advantage the team inoculated mice bred under sterile conditions, so they had no microbiome, with E. faecalis and a similar strain of bacteria sensitive to the phage it produces. Another group of the same mice were inoculated with the mutant E. faecalis, lacking prophage 7, and the phage sensitive bacteria. They monitored the number of bacteria of each type and found lower levels of the phage sensitive bacterium in mice with E. faecalis compared to the mice with the mutant E. faecalis. Confirming that producing the virus can give an advantage.

But can phage production be manipulated without negatively affecting E. faecalis? This could be important because if we could control the release of phages against different types of bacteria, for example the antibiotic resistant Clostridium dificile which can cause lethal diarrhoea, we could have a new antibacterial weapon. Or, if we could turn them off, a way to restore levels of an important ‘good’ bacteria whose numbers are being depleted for some reason.

To find out if this was possible they looked at the conditions E. faecalis was grown in in the lab. Various combinations of different things were tried but one condition stood out. When they added more amino acids—the building blocks of proteins—there was an increase in the number of phage made. When there were less amino acids, there was less phage, even though the bacteria grew normally.

The researchers are quick to point out that it’s difficult to be sure that this is what happens when E. faecalis is in the body or how big a part amino acids really play; there are likely be other factors at work, but it seems reasonable to expect that the availability of amino acids in the body will be one of them.

Viruses that naturally prey on bacteria and those released in a more measured way by bacteria themselves are promising ways to treat disease. But it is still at an early stage compared to the chemicals and proteins we currently think of, and use, as drugs.

Before we can get there, there is a long road ahead. Not only are there the viruses hiding out  silently in bacteria, released when conditions are right, there are also the viruses working to their own game plan. Of the millions of different microbe species that make up the microbiome that we are trying to understand, there are likely even more viruses capable of influencing and shaping its composition: the ‘virome’. Duerkop, B., Clements, C., Rollins, D., Rodrigues, J., & Hooper, L. (2012). A composite bacteriophage alters colonization by an intestinal commensal bacterium Proceedings of the National Academy of Sciences, 109 (43), 17621-17626 DOI: 10.1073/pnas.1206136109



Image credits:

Main image

Scanning electron micrograph of Streptococcus faecalis, Wellcome Images, Copyrighted work available under Creative Commons by-nc-nd 2.0 UK: England & Wales