Q&A: Professor Jeff Errington

Jeff ErrringtonNext month, Society member Professor Jeff Errington FRS will be awarded the prestigious Leeuwenhoek Medal by the Royal Society. The award, named after pioneering Dutch microscopist Antonie van Leeuwenhoek, is awarded triennially and recognises excellence in the fields of bacteriology, virology, mycology, parasitology and microscopy.

Professor Errington’s lecture will focus on his work on the fundamentals of bacterial cell division and how the bacterial cell wall – a flexible layer of proteins and sugars found in almost all bacteria – is important in cell shape. We caught up with him to ask about his work and about his forthcoming prize lecture.

How would you describe your research?

My long-term interests are on some of the most basic questions in biology: “What makes a cell a particular shape?”, “How do chromosomes get replicated and then pulled apart?”, “How do cells know where to divide, and how is division achieved?” I’m investigating the molecular basis for each of these processes. Answers to many of these questions – in bacterial cells at least – relate to cell wall synthesis. In order for bacteria to grow and divide correctly they have to be able to accurately manipulate their cell walls.

How does a bacterium achieve its desired shape?

We’ve found genes that if mutated interfere with a bacterial cell’s shape. The most famous of these genes is mreB, which is a homologue of actin, an important cytoskeletal or “scaffolding” protein found in eukaryotic cells. Before our work, people assumed that bacteria didn’t have cytoskeletons, but we now know they have many proteins that are used in a similar way to the cytoskeletal proteins found in eukaryotic cells, in the sense that they direct the shape of the cell, the division machinery, things like that. If you have a Staphylococcus it’s always a sphere and if you have a Bacillus it’s always elongated. The MreB protein, and the proteins it controls, are pivotal in determining the shape of a cell.

So MreB can perhaps be thought of as a ‘master switch’ – what sorts of things does it do?

Our original experiments with MreB revealed a spectacular helix structure that runs along the length of the bacterial cell, just below the membrane. On the basis of this we thought that MreB proteins had a direct structural role in determining bacterial cell shape. However, when you look in more detail you find that MreB is more sophisticated; the protein changes shape and rotates around the inside of a bacterial cell as it grows. We also know that MreB interacts with all the key proteins involved in cell wall synthesis.

What happens if you remove MreB completely? What does the cell look like?

The cells are really sick if you delete the mreB gene; Bacillus cells lose their rod shape and become spherical, which I guess is a bacterium’s default shape if you don’t have any proteins determining otherwise. The MreB protein seems to be a crucial part of the mechanism that imposes a non-spherical shape on a cell.

What will you be talking about in your award lecture?

The cell wall is incredibly important to bacteria: it is an essential structure for the microbes, but also a target for the best antibiotics that we’ve got. If you look at the genes involved in cell wall synthesis they’re found throughout the Bacterial domain. There are a few exceptions, but these appear to be a retrograde evolutionary step. Given their ubiquity, you’d imagine that the cell wall was probably present in the Last Common Ancestor (LCA) of the bacteria, from which all others evolved. One of the questions that became interesting to us is: how do cells survive if they don’t have a cell wall? There have been some reports going back many decades about ‘L-form bacteria’ that were supposed to be lacking a cell wall. These bacteria are thought to be clinically important, as treating people with antibiotics that inhibit cell wall synthesis leads to a selection for bacteria that don’t have a wall. We started studying L-forms of Bacillus subtilis and discovered that these cells are quite extraordinary. We now understand the genetic basis of L-form generation and found that these bacteria become independent of a whole slew of genes involved in cell division and cell wall synthesis. These genes are normally essential for growth, but they become completely non-essential in these L-forms.

The Mycoplasma are a genus of bacteria that are known for having no cell walls. What’s the relationship between them and L-form bacteria?

It’s likely that Mycoplasmas evolved from an L-form bacterium, which itself derived from a Clostridium. A Mycoplasma looks like an L-form that’s become more sophisticated and evolved in a new direction to take advantage of their lack of a cell wall.

Why are L-form bacteria important?

A big unanswered question is how important L-form bacteria are in infectious disease. The majority of clinical microbiologists don’t think about L-forms, even though there have been hundreds of descriptions of them in the literature. The problem is that many of these descriptions have been anecdotal case histories. For the first 40 or 50 years of L-form research, there was no molecular biology. It’s only with the advent of new techniques that we’ve been able to study them in more detail. We’re now working with clinicians to understand how important L-forms are medically.

Do you think these bacteria represent an under-diagnosed medical problem?

I think they probably do. There are several reasons why L-form bacteria are not identified very often. They grow very slowly and are very fragile; if you don’t put them in the right growth medium you just don’t see them at all.

It seems that L-form bacteria live in a very niche environment; what sort of places are they found?

People have found them in urine samples, blood samples, cerebrospinal fluid and they could be living in joints, but we don’t yet know, as there hasn’t been enough research undertaken. They might not be there at all! But either way, it would be good to know.

What can we learn from L-form bacteria?

My lecture title is Bacterial cell walls, antibiotics and the origins of life. The last part of the title alludes to the fact that L-forms, and the way they divide, may give us the answer to how early bacteria were able to divide, before the cell wall was invented by evolution. L-form division is very simple – all a bacterium has to do is produce an excess of membrane, it can then split in two in a process known as ‘blebbing’. We were very surprised by this mechanism – biophysicists have been looking at how simple vesicles might replicate and came to the same conclusion as us: increase surface area and you’ll get spontaneous division.

Will we ever know what the Last Common Ancestor looked like? Can we trace evolutionary history back that far?

I think with further advances in informatics we can get a pretty good idea of what the LCA looked like. Actually, I think the LCA would have had a cell wall, despite what I’ve said! Floppy, wall-less cells can fuse as well as divide, so it would have been very difficult for such a microbe to maintain a stable genome. I recently wrote a review for Open Biology in which I speculated that the invention of the cell wall was a defining event that allowed the bacterial kingdom to explode.

Professor Errington’s Leeuwenhoek Lecture will be held at the Royal Society on 17 March 2015 from 6.30-7.30 pm. Doors open at 6pm and attendance is free. More details can be found here.

Professor Errington was interviewed by Benjamin Thompson

Image credit: Jeff Errington
This entry was posted in Microbial Evolution and Diversity and tagged , , , , . Bookmark the permalink.

One Response to Q&A: Professor Jeff Errington

  1. Pingback: Best of the blog 2015 | Microbe Post

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