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Lab Rat

Lab Rat

Exploring the life and times of bacteria

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.

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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

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

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