Magnetotactic bacteria

Marina Polyakova, "Elements"

The photo taken with a scanning electron microscope shows the magnetotactic bacterium Magnetococcus marinus. Canadian scientists have learned to use her natural abilities to effectively fight cancer. They "armed" her with liposomes with an antitumor drug. And then, using the magnetotactic properties of this bacterium, they sent it directly to the center of the tumor. Photo from the article O. Felfoul et al., 2016. Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions.

But let's take it in order. Living organisms have many mechanisms for orientation in space. Plants use sunlight and gravity to determine in which direction to grow, birds during migration are partially guided by the location of the sun and stars, well, you can just ask a passerby for directions.

Some animals use the Earth's magnetic field for navigation. They have something like a built-in compass that will always tell you the way. This method can be used by both large organisms like fish or birds, and the simplest ones. For example, some types of bacteria have magnetotaxis, and for this they are called magnetotactic.

Magnetotactic bacteria are found in almost all classes of the group of proteobacteria (Proteobacteria) and Nitrospirae. All of them belong to gram-negative bacteria: their cell membrane is two-layered, unlike the single-layered one in gram-positive bacteria. They are found everywhere in fresh, brackish and marine reservoirs. Most magnetotactic bacteria are mesophiles, that is, they live at temperatures from 20 °C to 45 °C. However, in the hot springs in northern Nevada (USA), the bacterium HSMV-1 from the Nitrospirae group was discovered, which can exist at a temperature of about 63 ° C – that is, a classic thermophile. Several alkaliphilic (loving high alkalinity) species have also been found.

Magnetotactic bacteria were first discovered in 1975 by microbiologist Richard Blakemore (not to be confused with guitarist Richie Blackmore from Deep Purple!). He studied swamp mud samples under a microscope and noticed the strange behavior of some bacteria. Instead of randomly rushing back and forth across the slide, they were heading in the same direction, towards the window. At first, the scientist decided that it was the sunlight from the window and that it was the bacteria that reacted to it. But moving the microscope to another room did not change anything – the direction of movement remained the same. Then Blakemore suggested that the bacteria could move to the north – that's where his window looked out. He tested his theory with a magnet and couldn't believe his eyes: the bacteria reacted to the magnetic field! When the scientist brought a magnet to the microscope, the microorganisms rushed towards its northern end, forgetting about their previous trajectory. And as soon as the magnet was removed, they began to move again towards the north magnetic pole of the Earth.

How do they do it? Magnetotactic bacteria have small organelles – magnetosomes. They arise as a result of the bulging of the inner membrane of the cell and the formation of empty vesicles - vesicles. After the formation of vesicles, a process of biomineralization occurs, in which a large amount of iron accumulates in them. Depending on the growth conditions, more than 99.5% of the total intracellular iron of the cell may be present in magnetosomes, which, in turn, may account for more than 4% of the dry mass of the cell.

The exact way iron gets into the vesicles is unknown, but there are two most likely ways. The first one assumes that iron enters the vesicle lumen from the periplasm – the space between the inner and outer membranes of the cell when the magnetosomal membrane is still part of the cytoplasmic membrane.

The second way of delivering iron ions to vesicles is the use of special transporter molecules. First, some molecules "take" these ions on the cytoplasmic membrane and launch them into the cytoplasm, then other transporters transfer iron through the magnetosomal membrane from the cytoplasm into the future magnetosome.

The diagram shows two possible ways of delivering iron (Fe) to the vesicles of magnetosomes. The first method is directly from the periplasm through the lumen in the cavity of the vesicle. The second is through the cytoplasm using special transporter molecules (orange and blue figures). OM is the outer layer of the cell membrane, IM is the inner layer. A drawing from the article by L. Rahn-Lee, A. Komeili, 2013. The magnetosome model: insights into the mechanisms of bacterial biomineralization

Soon after the vesicles are filled with iron, the cell turns them into crystals of magnetite or its sulfide analogue greigite. The magnetic moment of magnetite is several times greater than that of greigite. This is probably due to its popularity among magnetotactic bacteria. Each crystal is a magnet with a north and south pole. Bacteria stack the crystals inside themselves in one chain and fix them with a special structural protein to make one long magnet (just like the arrow of a compass). The more crystals there are, the stronger and more sensitive the magnet is to the magnetic field. This design is used by bacteria to orient movement along the Earth's geomagnetic field.

Interestingly, during cell division, the chain of magnetosomes divides exactly in half – part remains with the mother cell, and part goes to the daughter cell. Then, in the process of growth, they absorb iron from the environment and both lengthen their magnetosomes to the required length.

Magnetotactic bacterium with magnetosomes (dark dots). In the center is an enlarged magneto image. In the middle of the magnetosome there is a magnet particle covered with a magnetosomal membrane (the result of protrusion of the inner cell membrane). In a single chain, the magnetosome complex is stabilized by the MamA protein. Figure from the article N. Zeytuni et al., 2011. Self-recognition mechanism of MamA, a magnetosome-associated TPR-containing protein, promotes complex assembly

Why do bacteria need a compass? Like many other types of bacteria, magnetotactic bacteria do not like oxygen very much and prefer to live in environments where its concentration is as low as possible. Most of them are microaerophiles: they need oxygen for normal growth, but in small quantities. The excess has a negative effect on these bacteria, and they always tend to avoid areas with an increased concentration of it. Therefore, their favorite place of residence is on the border of the oxygen and oxygen–free zone in reservoirs. They use their natural compass to determine where the bottom is and where the top is, vary the depth of immersion and, thus, choose the most favorable conditions for themselves.

There are also anaerobic species that do not tolerate oxygen in any amount. They also use magnetotaxis to swim as deep as possible, into an oxygen-free zone. Just among such bacteria, greigite lovers are most often found, since oxygen is not required to create it.

The Earth's magnetic field is oriented more or less vertically everywhere except the equator. Therefore, magnetotactic bacteria, guided by the Earth's magnetic field, migrate faster and easier to areas with low oxygen content than those bacteria that randomly float in all directions. In the Northern Hemisphere, bacteria tend to the magnetic north, and in the Southern hemisphere – to the south (recall that the magnetic and geographical poles of the Earth do not coincide).

The direction of the Earth's magnetic field and the orientation of magnetotactic bacteria in the Northern and Southern hemispheres. A drawing from the article by S. Hussain, 2016. Nature's Living Magnets: An unexpected tool to treat disease

The orientation of magnetotactic bacteria is based on a combination of magneto- and aerotaxis. Magnetotaxis is responsible for the bacteria to swim to a depth – the deeper, the less oxygen – or up if oxygen becomes insufficient. Aerotaxis monitors its concentration and determines that the conditions are already quite comfortable and it's time to stop.

On the left is a diagram of a water column divided into oxygen (Oxic), oxygen–free (Anoxic) and intermediate (OATZ – oxic–anoxic transition zone) zones. On the right is an enlarged intermediate zone, which shows magnetotactic bacteria. They use their magnetosomes to move along the magnetic field lines (dotted arrows) and reach the zone with the optimal oxygen concentration. An illustration from an article by D. H. Nies, 2011. How iron is transported into magnetosomes

Scientists are interested in the practical use of magnetic bacteria. Of course, they will not attach a love message to the refrigerator, but you can find a lot of other useful uses. For example, as mentioned at the beginning of the article, Canadian researchers have shown that magnetotactic bacteria Magnetococcus marinus can be used to deliver drugs deep into hypoxic (containing little oxygen) areas of tumors. M. marinus, like most magnetotactic bacteria, has flagella for active movement in the aquatic environment. These little tail-like structures can rotate and work like a propeller, allowing the bacteria to swim quickly and change direction easily. In addition, the spherical shape and small size (1-2 microns) allows them to easily squeeze into the narrow (about 2 microns) intercellular spaces in the tumor.

Using antibodies, scientists attached tiny bubbles (liposomes) with the antitumor drug SN-38 inside to the outer membrane of M. marinus. Then bacteria were injected into laboratory mice in the tissue near the tumor. Having created a three-dimensional magnetic field, they used a special magnetic platform to direct the movement of microorganisms "armed" with liposomes with the drug as close as possible to the tumor, so that they could detect the oxygen concentration gradient. After that, aerotaxis came into play. The bacteria, "sensing" the difference in oxygen content, rushed towards its lowest concentration, that is, to the center of the tumor. As a result, more than half of the bacteria delivered the medicine to the destination.

This method can not only reduce the risk of relapses, but also reduce  the toxicity of the treatment, since the drugs will not spread throughout the body, but only to where the bacteria will deliver them.

And finally, a video about how scientists made bacteria dance.

Magnetic bacteria can be useful not only in serious matters, but also as a scientific entertainment. Dutch and German scientists made bacteria dance in a superimposed magnetic field

Portal "Eternal youth" http://vechnayamolodost.ru  11.09.2017