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 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
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Pathways of resistance: from mercury to methicillin

ResearchBlogging.orgMercury BeadIn a climate of rising fear over the diminishing efficacy of antibiotics, microbiologists from the Universities of Nottingham and East Anglia have looked back at the bacteria-killing substances of the pre-antibiotic era: metals. Dr Jon Hobman and Dr Lisa Crossman’s review, published in the Journal of Medical Microbiology, concludes that the ancient pathways of resistance which bacteria have evolved against these metals may be intimately linked to the antibiotic resistance genes that are circulating in bacterial populations today.

Metals and metallic compounds have been used for medical and biological purposes for millennia: as antiseptics, diuretics, and dental fillings; cosmetics, tonics and chemical weapons. Most are indiscriminately toxic, and you wonder whether some of these historical cures were actually worse than the ailments they were intended to treat – mercury-laced teething powder, anyone?

Metals and their ions can damage cells in multiple ways: binding to enzymes, DNA and membranes, disrupting their function; taking part in reactions that generate harmful free radicals; or binding to the cell’s pool of antioxidants that usually protects against free radicals. It is the lethal damage that these mechanisms can inflict on bacterial cells that underlies the utility of metal compounds in controlling infections in plants, animals and humans. Continue reading

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New to Science – February 2015

Each month, the Society for General Microbiology publishes the International Journal of Systematic and Evolutionary Microbiology, which details newly discovered species of bacteria, fungi and protists. Here are a few of the new species that have been discovered and the places they’ve been found. The full papers are available to journal subscribers, but the abstracts are free to read.

It is the Society for General Microbiology’s 70th birthday this month – it was formally inaugurated on 16 February 1945 and Sir Alexander Fleming became its first President. Such anniversaries are always a time for reflection on the past and its lessons and challenges.

Microbiologists from South Africa and Italy undertook a similar journey into the past, providing New to Science with the most unusual microbe discovery location we have seen so far. The researchers were studying the damage caused by microbial communities in the catacombs of St Callixtus in Rome, which were founded in the very earliest years of Christianity and once housed the tombs of many popes from the first millennium AD. Here, the researchers isolated Kribbella italica from a biofilm growing on the walls of one of the tombs. Continue reading

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Antibiotic resistance transfer: where’s the culprit?

ResearchBlogging.orgColorized low-temperature electron micrograph of a cluster of E. coli bacteriaEscherichia coli is a species of bacteria that forms an essential part of the gut microbiome of many warm-blooded animals, including humans. Most strains are completely harmless to us, but some cause diseases including food poisoning and urinary tract infections. A group of antibiotics known as cephalosporins are often used to treat harmful E. coli infections, but some strains of the bacterium produce substances called extended-spectrum beta-lactamases (ESBL) that confer immunity to these antibiotics.

ESBL-producing E. coli used to be most commonly found in hospital environments, but they are now increasingly causing infections outside of hospitals, as well. The presence of such bacteria in the meat we consume is thought to contribute to the rising prevalence of community-acquired infections. After all, antibiotics are used heavily in the farming industry, so the development of resistant bacterial strains is to be expected.

Previous studies concluded that the ESBL-producing E. coli strains found in farm animals, retail meat and humans were extremely similar, suggesting that consumption of contaminated meat had allowed the bacteria to spread to humans. However, as Mark de Been, a bioinformatician at the Utrecht Medical Centre, explains, this research was based on studies of only a small part of the bacterial genomes. de Been is the lead author of a new study recently published in the journal PLOS Genetics, which shows that the bacteria found in animals and humans are actually significantly different. Continue reading

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Microbe Talk: January 2015

527049831Imagine waking up tomorrow morning to find out that every bacterium and every archeon on the planet had suddenly vanished. What would happen? Could humanity survive? This month, Ben spoke to Dr Jack Gilbert and Dr Josh Neufeld, who have published a thought experiment in PLOS Biology that wonders exactly that…


Show notes:

Don’t forget, you can subscribe to Microbe Talk on iTunes. You can also find us on Stitcher.

Benjamin Thompson

Image Credit: Thinkstock
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World Leprosy Day 2015

World Leprosy Day 2015Leprosy is among the oldest human-specific infections we currently know about. The common ancestor of the two modern bacterial species that cause leprosy, Mycobacterium leprae and M. lepromatosis, is thought to have become a parasite in early humans millions of years ago. This makes it far older than our own species, Homo sapiens. Nevertheless, leprosy continues to afflict hundreds of thousands of people every year.

World Leprosy Day raises awareness of the suffering caused by the disease. It remains endemic in India, where more than half of all worldwide cases occur, and in parts of South East Asia and Africa. World Leprosy Day is observed on the last Sunday of January to coincide with the anniversary of the assassination of Mahatma Gandhi, a vocal supporter of the fight against leprosy.

What is leprosy?
Leprosy is a chronic bacterial infection caused by two members of the genus Mycobacteria. It is usually thought to be transmitted between people via droplets when people breathe or cough, although armadillos may also play a role in transmitting the disease to humans.

Despite its continued prevalence, leprosy is actually one of the least infectious diseases we know. Globally, only about 5% of people are actually susceptible to leprosy due to a malfunction in the gene responsible for conferring immunity; the rest of the human population is immune. Furthermore, of the clinical cases that do occur, some 85% are non-infectious.

The number of new leprosy cases – roughly 200,000 a year – is all the more remarkable given the low risk of acquiring and transmitting the disease. Continue reading

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Crimean-Congo Haemorrhagic Fever: A Phantom Menace

ResearchBlogging.orgA tick Hyalomma marginatum on human skin.Viral haemorrhagic fevers are a poorly understood group of diseases, but they have entered the public consciousness in unprecedented fashion due to the Ebola outbreak in West Africa. The viruses that cause these diseases are transmitted by a range of vectors that can include primates, rodents and insects. They rely on these animals to survive and don’t always pose a risk to them; however, the viruses cause disease when they infect humans. A team of researchers at Public Health England’s Porton Down laboratories have now studied the Crimean-Congo Haemorrhagic Fever virus (CCHF) and developed a new vaccine against the disease, which infects up to 1,500 people each year and kills between 10-40% of them. We spoke to lead author Dr Karen Buttigieg to find out how they did it.

CCHF: a brief introduction
Like many viruses, Crimean-Congo Haemorrhagic Fever, or CCHF, is named after the place – or, in this case, places – it was first discovered. The virus was first identified by Soviet scientists in 1944 and provisionally named Crimea virus, although they could not isolate the virus to formally describe it until June 1967. However, four months earlier, a virus called Congo virus had been officially described in the East African Medical Journal – and the two turned out to be identical. Because the Congo virus discovery was published first, the International Committee on Taxonomy of Viruses proposed the name Congo-Crimean Haemorrhagic Fever virus. However, Soviet authorities insisted on the Crimean-Congo nomenclature and as a result of the extreme tensions of the cold war at the time, this variant of the name was adopted. This remains one of only a handful of virus name changes as a result of political pressure.
Continue reading

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