Saturday, June 9, 2012

Helical bacteria: the benefits of being twisted

One of the first things you learn in bacteriology is that bacteria come in different shapes. Not a huge range of shapes admittedly, but the main shapes are spherical, rod-shaped, or spiral. Spherical bacteria make sense ? a sphere has the largest surface area for a given volume which means that the bacteria can absorb as many nutrients from the outside world as possible and easily diffuse them throughout the cell. Likewise a rod is a good shape for bacteria that move around a lot, giving them more propulsion through crowded spaces (and when you?re small enough to be on the same scale as large molecules, every space is crowded).

Different bacterial shapes (from wikimedia commons, credit link below). A: rod shaped "bacci" bacteria B, C and D: spherical "cocci" bacteria, E: spiral bacteria, F: bacteria with stalk or budding appendage

But why spirals? What benefits do bacteria gain from being shaped like a corkscrew?

I was quite excited therefore, to see two recent articles in PLoS Pathogens that both addressed this issue. One concerned the bacteria campylobacter jejuni (which causes bacterial-induced?diarrhoea) and one was on?helicobacter pylori (the bacteria that causes stomach ulcers, which I?ve written about previously).?In both cases the helical shape can be destroyed by fairly simple gene knockouts, and in both bacteria the loss of the helical shape resulted in a decrease in virulence and the ability of the bacteria to function within a body.

Starting then with c. jejuni, which I have a soft spot for because I worked with it back when I was studying bacteriophages.

Scanning electron micrograph of Campylobacter, clearly showing the spiral shape. Photo by De Wood; digital colorization by Chris Pooley, credit link below.

So first of all, how to remove the spiral shape from the bacteria. Researchers in reference 1 found one gene, which they called?pgp1 (peptidoglycan peptidase 1), which when deleted turns the bacteria from a neat little spiral into a boring rod shape. As its name suggests pgp1 acts on peptidoglycan, which is a major component of the bacterial cell wall. When deleted, the resultant rod-shaped bacteria are three times worse at colonising chicks (C. jejuni is also a major causes of diseases in chickens) and are also bad at forming biofilms and generally moving around. Figure 1 in the reference has some excellent pictures of the spiral bacteria and the sad rod-shaped mutants.

There were no differences between normal c. jejuni and pgp1 mutants when it came to growth, stress survival or general living on nutrient agar; the spiral shape only seems to have an effect on factors important for virulence and survival inside a body. The researchers also made mutants that overexpressed the pgp1 and found that this too had a straightening effect on the cells (again, lovely bacteria pictures in figure 3). When they took the pgp1 gene and put it into a normally rod-shaped bacteria (E. coli) there was no change in shape. The corkscrew-effect the pgp1 produces is only present when the gene is in C. jejuni and expressed at the correct levels, which is a pity because spiral shaped E. coli would be cool.

So the spiral-shape in C. jejuni seems to be controlled by one major gene (probably with the help of a few others) and is important for pathogenicity. What about H. pylori?

Scanning electron micrograph of Helicobacter pylori, showing the spiral shape. Image from the National Institutes of Health, part of the United States Department of Health and Human Services. Credit link below.

In h. pylori the story is slightly different. Previous research in bacteria which had lost their helical twist (although they still maintained a slightly curved shape, hold that thought) showed no difference in movement or swimming motility. H. pylori live in the mucus lining of the stomach, and it was thought that the helical shape would it to push through this viscous material more easily. The less-twisty bacteria did still show a difference in colonisation ? the twisted wildtype bacteria were much more likely to colonise the stomach lining than the straighter mutants.

In reference 2, the found a new gene (csd4) involved in the curved shape of the bacteria, which the original non-twisty mutants still maintained. It turns out that if you knock out this gene from the non-twisty mutants the bacteria loose all traces of curve or twistyness and movement through viscous solutions that mimic the stomach lining is a lot harder. Unlike C. jejuni therefore, the H. pylori have two genetic mechanisms that cause the helical shape. One gene that causes the helical twist by crosslinking bits of the cell wall and another (the csd4 identified in reference 2) that independently induces curving of the cell. These two mechanisms do appear to be completely independent as well, and both contribute to increase twistyness of the cell.

So while C. jejuni has one gene solely responsible for the spiral shape and increased virulence, H. pylori has two. There may be environmental reasons for this (C. jejuni can survive in a larger range of hosts) however as they are rather unrelated bacteria is may just be that the helical-shape has existed for longer in H. pylori which has picked up more than one mechanism to produce it (and if anyone is aware of any more reasons, do email me and let me know!). What is clear is that bacteria have very firm reasons for being the shapes they are, and those shapes are not limited?solely?to spherical blobs.

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Credit link for image 1 (bacterial shapes)

Credit link for image 2 (campylobacter)

Credit link for image 3 (helicobacter)

Reference 1: Frirdich E, Biboy J, Adams C, Lee J, Ellermeier J, Gielda LD, Dirita VJ, Girardin SE, Vollmer W, & Gaynor EC (2012). Peptidoglycan-modifying enzyme Pgp1 is required for helical cell shape and pathogenicity traits in Campylobacter jejuni. PLoS pathogens, 8 (3) PMID: 22457624

Reference 2: Sycuro LK, Wyckoff TJ, Biboy J, Born P, Pincus Z, Vollmer W, & Salama NR (2012). Multiple peptidoglycan modification networks modulate Helicobacter pylori?s cell shape, motility, and colonization potential. PLoS pathogens, 8 (3) PMID: 22457625

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