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The bacteria that use cholesterol to get into cells.

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Although it usually only gets talked about when it starts causing problems, cholesterol is an important molecule to have in the body, as it is a component of cell membranes. The major component of cell membranes is a molecule called a phospholipid; an inorganic phosphate molecule joined onto lipid tails. Lots of these phospholipids all line up to form the cell membrane. Cholesterol is another lipid molecule, which fits in between the phosopholipids and can influence the membranes permeability and fluidity.

Diagram of the membrane that surrounds human cells. The two layers of phospholipids can be seen (blue and while spheres with the lipid tails pointing inwards) studded with bright red proteins. The yellow blobs within the phospholipid layer are cholesterol. Image from the National Institute of Standards and Tchnology - link below

There are two ways cells can get hold of the cholesterol needed for the membranes, by using food sources containing low-density lipoproteins (LDL), or by synthesising it within the cell. Defects in the cholesterol synthesis pathway can increase the likelihood of the cell breaking down through apoptosis or due to oxidative stress. Around 20-25% of the cell membrane is made up of cholesterol in mammalian cells.

Despite the above diagram, the phosolipid molecules are not rigidly stuck in place within the cell membrane, as long as they keep the phosphate facing outwards and the tails inwards both they and the steroids can travel around the membrane. This means that some areas will gather clumps of cholesterol, known as lipid rafts, which play important roles in cell signalling, membrane shape, and of course, bacterial invasion. Many bacteria target these lipid rafts when looking for places to attach onto human cells, and they act as the first point of cellular invasion.

Researchers found that limiting the amount of cholesterol in the mammalian cell membrane (by blocking the internal cholesterol synthesis pathway) led to far less effective invasion of bacteria and bacterial toxins. The diagram below shows an electron micrograph of mouse tissue, in the one on the left the cells cannot make cholesterol and in the one on the right the cells have normal cholesterol-making activity. Little black arrows show where the toxins produced by the cholera bacteria have been taken up by the cells.

Scale bar = 500 nm. Image from reference 1.

Only 9% of −cholesterol cells contained 10 or more toxin-containing vacuoles, compared to 80% of the +cholesterol cells.

Repeating the assay shown above with different bacterial strains revealed that the bacteria C. burnetii also require cholesterol to enter the cells,  while Salmonella typhimurium and Chlamydia trachomatis enter both cholesterol and non-cholesterol containing cells at the same rate. While lipid rafts are required for cell entry by some bacteria, it seems that others do not seem to rely on them.

(A). The number of internalized C. trachomatis was unchanged between −cholesterol and +cholesterol calls. In contrast, internalization of C. burnetii was decreased by 87% (p = 0.0009) in −cholesterol calls. (B). Wild type S. Typhimurium and a mutant without the Salmonella toxins invaded −cholesterol and +cholesterol cells with equal efficiency. Image from reference 1.

The researchers suggest that as well as affecting bacterial cell attachment to the cell surface, the cholesterol may also be vital for the uptake of certain bacteria and their internal transport. It may therefore be possible that the cholesterol is not only important for helping bacteria enter the cells, but also for their further growth and development inside the host cell.

The particularly interesting thing about this research was the method used to remove cholesterol from the cells. Because it is such an important membrane component, chemical methods tend to drastically alter the shape of the cells which causes more problems for bacteria trying to get in. For this paper, the researchers instead targeted the cholesterol synthesis pathway, removing the final enzyme. This system therefore allows a cholesterol-free environment to be explored without causing any significant changes to the cell membrane integrity.

Credit link for image 1

Reference 1: Gilk SD, Cockrell DC, Luterbach C, Hansen B, Knodler LA, et al. (2013) Bacterial Colonization of Host Cells in the Absence of Cholesterol. PLoS Pathog 9(1): e1003107. doi:10.1371/journal.ppat.1003107

S.E. Gould About the Author: A biochemist with a love of microbiology, the Lab Rat enjoys exploring, reading about and writing about bacteria. Having finally managed to tear herself away from university, she now works for a small company in Cambridge where she turns data into manageable words and awesome graphs. Follow on Twitter @labratting.

The views expressed are those of the author and are not necessarily those of Scientific American.

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  1. 1. naya8 12:18 am 01/28/2013

    Very interesting.Most interesting for me is to know the same pattern for mycoplasma, since this bacteria has a membrane only without cell wall. And more than that; this bacteria needs lot of colesterol or glecerole to servive.

    Link to this
  2. 2. CharlieinNeedham 12:32 am 01/29/2013

    If this is really true: “Around 20-25% of the cell membrane is made up of cholesterol in mammalian cells.”

    … then is it really likely that their findings “limiting the amount of cholesterol in the mammalian cell membrane (by blocking the internal cholesterol synthesis pathway) led to far less effective invasion of bacteria and bacterial toxins”

    … has a practical application in living mammals?

    That is, if cholesterol seems to be such a vital component of cell membranes, can cholesterol be eliminated in a living organism without causing cellular death from a breakdown in the integrity of the cell membrane?

    Furthermore, since “clumps of cholesterol, known as lipid rafts, which play important roles in cell signalling, membrane shape, and of course, bacterial invasion”
    … would the loss of cell signalling be so profound, that even if cell membrane could be maintained, the mammal would die from the loss of vital roles of cell signalling?

    Very interesting science.

    It just seems a pity there seems to be little practical application.

    Link to this
  3. 3. S.E. Gould in reply to S.E. Gould 4:25 am 01/29/2013

    Thanks for your comments!
    @naya8: It would be interesting to find out about the mycoplasma, I suspect their membranes will also contain cholesterol. I’m not sure whether it would necessarily be more cholesterol than the average membrane, but it would be interesting to see!

    @charlie: You are correct in that removing the cholesterol from cell membranes would be disastrous, however that does not mean that this research is useless for practical purposes. The researchers were not exploring whether the removal of cholesterol could be a potential antibacterial measure, they were gathering more information about bacterial cellular invasion, which helps to build up a complete picture of disease. The more complete the picture, the more correct that models looking for treatment will be. It takes a lot of time to do research, and not every paper will show a revolutionary new way to fight bacteria.

    There was thought to be very little practical application in studying bacteria that live in hot thermal springs. But a particular DNA polymerase enzyme isolated from one turned out to be ideal for doing PCR – a technique which is now indispensable for genetic research. Sometimes you never know when a practical application will arise!

    Link to this

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