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A new study published in the journal Nature in March 2020 reports on a unique transporter protein found in the bacterium Mycobacterium tuberculosis.Unlike other transporters, this giant transmembrane vesicle protein helps carry hydrophilic molecules, especially vitamin B12 or cobalamin, across cell membranes.
The research is based on using cryo-electron microscopy to obtain images of transporters.Tuberculosis is a complete organism because it has all the necessary genetic machinery to produce cobalamin in its cells.However, it must receive vitamins from the outside for successful cell division.
To accomplish this, it uses a vitamin B12 transporter, one of a large family of ATP-binding cassette (ABC) transporters.These proteins use the chemical energy stored in ATP molecules to carry substrate molecules across cell membranes.These transporters are also involved in the transport of peptides such as bleomycin, which inhibit the growth of microorganisms.This is a curious phenomenon, says researcher Dirk Slotboom, who says two very diverse molecules are rarely carried by the same transporter.
This prompted the current study to examine the structure of this unique protein.”‘It was a long process, but we ended up cracking it using cryo-electron microscopy,’” Slotboom said. The results were striking: The protein contained what could only be described as gigantic, a large cavity filled with water that extended into the cell membrane The entire width, the capacity is 7,700 cubic angstroms – as many as seven cobalamin molecules, according to the researchers.
The transporter’s job itself seems simple: just empty itself and put everything in the water.Hence the sluice analogy.”You’re letting in the water and everything in it,” Slotboom goes on to explain. This may be how it can transport vitamins and antibiotic peptides at the same time, although their structures are very different.
Non-selective transport capabilities also have their drawbacks, the most obvious of which is inefficiency.However, this is not a problem in this case, the Bacillus only needs to take up a limited number of cobalamin molecules to complete its reproductive cycle which lasts about 24 hours.
The researchers were surprised by the difference between this transporter and any other known conventional transporter.They commented: “It changes the way we look at bacterial physiology. There are strong indications that other bacterial species have similar systems, meaning that they acquire molecules randomly from the environment.”
On the other hand, researchers are intrigued by the possibility that human cells may also have very similar mechanisms for transporting substances such as cobalamin.This vitamin first binds to a gastric peptide called intrinsic factor.This peptide comes from specialized parietal cells in the stomach lining and allows vitamin B12 to form a complex with it.The complex is then taken up by epithelial cells.
This complex eventually settles in lysosomes within epithelial cells.Lysosomes are “suicide bags” filled with powerful enzymes.Here, intrinsic factor is broken down and B12 is released from the lysosome into the cell.Here, it is ultimately involved in the metabolism of cells.”I strongly suspect that a similar nonspecific transporter is involved,” Slotboom said.
Scientists also think they may be able to stimulate the activity of the cobalamin-bleomycin transporter to help treat tuberculosis.They said, “‘If we could stimulate the activity of this transporter, it might be possible to introduce antibiotics more efficiently and thus kill these cells more easily. However, we realised that this might not be simple, as bacteria use effective strategies to keep the antibiotics out.”
To do this, the scientists are next analyzing how the transporter works.The current hypothesis is that “inside the cell, the floodgates are emptied by binding and hydrolyzing ATP. But we don’t know how it opens on the outside to let in new molecules.”
Dimeric transporters consist of two halves.These appear to protrude to the outside of the cell membrane, and it’s possible that they open in some way, such as a door, to allow fresh cargo into the cell.The scientists wanted to see if they could somehow stimulate this opening or loosening process, thereby increasing the entry of antibiotics.
References: S. Rempel, C. Gati, M. Nijland, C. Thangaratnarajah, A. Karyolaimos, JW de Gier, A. Guskov, and DJ Slotboom: Mycobacterial ABC transporters mediate the uptake of hydrophilic compounds.Nature, March 26, 2020, http://dx.doi.org/10.1038/s41586-020-2072-8
Tags: antibiotics, B cells, bacteria, cells, cell division, cell membranes, electrons, electron microscopy, genetics, laboratory, lysosomes, membranes, metabolism, microscopy, molecules, peptides, physiology, proteins, stomach, T cells, tuberculosis , vitamin B12, vitamin
Dr. Liji Thomas is an Obstetrician and Gynaecologist who graduated from the Government Medical College, Calicut University, Kerala in 2001.Liji worked as a full-time consultant in obstetrics and gynecology at a private hospital for several years after graduation. She has consulted hundreds of patients facing pregnancy-related issues and infertility, and has overseen over 2,000 deliveries, always striving for normal delivery rather than surgery.
Thomas, Li Ji.(24 March 2020).Scientists have discovered that tuberculosis bacteria transport vitamins into cells.News – Medical.Retrieved 18 May 2022 from https://www.news-medical.net/news/20200324/Scientists-discover-tuberculosis-bacterium-channels-vitamins-into-the-cell.aspx.
Thomas, Li Ji.”Scientists discover that tuberculosis bacteria transport vitamins into cells”.News – Medical.May 18, 2022..
Thomas, Li Ji.”Scientists discover that tuberculosis bacteria transport vitamins into cells”.News – Medical.https://www.news-medical.net/news/20200324/Scientists-discover-tuberculosis-bacterium-channels-vitamins-into-the-cell.aspx.(Accessed 18 May 2022).
Thomas, Li Ji.2020. Scientists discover Mycobacterium tuberculosis transports vitamins into cells.News-Medical, viewed May 18, 2022, https://www.news-medical.net/news/20200324/Scientists-discover-tuberculosis-bacterium-channels-vitamins-into-the-cell.aspx.
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Post time: May-18-2022
