Bacterial study gives fresh insights on diabetes and fibrosis

The bacterium Thermus thermophilus, as the word suggests is heat loving, thermo means heat and philus means loving; so it is not surprising that you can find it in hot springs. In order to survive the extreme environment, the bacterium utilizes many kinds of carbohydrates for energy. Carbohydrates must be taken into the cell and broken down inside the cell into glucose to fulfill the energy needs.

Carbohydrates being big molecules cannot penetrate the cell membrane of cell. This can be understood like if somebody doesn’t know how to swim, they need some boat or rubber tube to cross the river, likewise carbohydrates also need some special helpers or transporting molecules to cross the cell membrane. So they use ABC transport system, which is one of the active transport system of the cell. Is the ABC transport system in this bacterium inherently selective to specific carbohydrates or does it have no such preference?

To answer this Indian Institute of Technology (IIT) Guwahati researchers have shown how some specialised protein molecules found on the cell membranes of all biological cells carry carbohydrate molecules into cells from outside.  They have studied specific protein molecules called ABC transporters, present in bacterial cell membranes and have shown that these transporters are selective about the type of carbohydrates they transport into cells.

These results offer a better understanding of how carbohydrates are taken into cells.  Defective transport of carbohydrates into cells is associated with a range of disorders, including cystic fibrosis, hypercholesterolaemia and diabetes. Understanding the mechanism of carbohydrate transfer by the ABC transporters would enable better understanding of the causes and effects of many of these disorders.

“Based on the preliminary analysis of the ABC transport systems of the bacteria we chose, we hypothesized that it would have different affinities for different carbohydrates”, says Dr Shankar Prasad Kanaujia, Associate Professor, Department of Biosciences and Bioengineering, IIT Guwahati. To validate this hypothesis, the team used X-ray crystallography techniques to determine the three-dimensional crystal structure of the ABC transport system connected to various types of carbohydrates having different kinds of glycosidic bonds.

“One of the largest classes of transporting molecules is the ATP-Binding Cassette (ABC) transporter, which is widespread in all forms of life”, says Dr. Kanaujia.  These special forms of proteins present in the cell membranes of almost all living cells, capture the carbohydrates from outside the cell and deliver them into the cells.

Table sugar and starch are only two of the numerous carbohydrates that are used by the cells, and they have to be preferentially taken into the cell.  While ABC transporters have been known for a long time, it remains unknown if these carbohydrate-ferries have preference for specific carbohydrates over others.

Many of the carbohydrates have similar structures and components, and differ in a specific type of bond or linkage, called glycosidic bonds.  There are two types of glycosidic bonds – alpha and beta. Dr Kanaujia told “We did not know if the ABC transporters have preference for any specific type of glycosidic bond”.

“The specific ABC transporters we studied had increased affinity to the alpha-glycosidic bonds”, said Dr Kanaujia. The team also found an interesting phenomenon – the transporters had a higher affinity for simple glucose than complex carbohydrates, which meant that any glucose in the extracellular space would be preferentially taken into the cells over higher carbohydrates.

The research team includes Dr. Shankar Prasad Kanaujia, Monika Chandravanshi and Prerana Gogoi. The results of this study have been published in The FEBS Journal.

(With inputs from India Science Wire)