One of the most important discoveries of the modern world is antibiotics. In the past, even a small injury could kill people, this problem has now disappeared. After the chance discovery of penicillin, many natural by-products antibiotics have been discovered.How far can these discoveries be made, and how long they can survive antibacterial resistance?
Developing antibiotics is not a very profitable business model today, so pharmaceutical companies have focused on other areas. As a result, the number of discoveries in recent years has decreased to almost 0.
Many of the antibiotics discovered are actually weapons used by bacteria or fungi. These weapons were developed to conserve limited resources. For example, alcohol is an antibacterial molecule produced by bacteria.
Discovering antibiotics with today’s classical methods is expensive and time consuming. The information of millions of molecules is stored in chemical libraries, but the properties of these molecules are not fully known.
Testing millions of molecules in the classical laboratory is very difficult in terms of physical facilities, so a new method must be developed. Computers can operate tirelessly and very quickly, if they can learn to predict chemical properties, the problem of physical limits will be eliminated.
Machine learning processes generally follow similar stages, sufficient and appropriate data, a machine learning method suitable for the target and reaching the desired function.
Steps researchers followed in the discovery of antibiotics:
Drug repositioning aims to use existing drugs in new therapeutic areas. In drug discovery, new molecules that have not been synthesized before can be found within the possibilities permitted by the laws of chemistry and physics, or previously known molecules can be used for new therapeutic purposes.
This study is an example of drug retargeting.Halicin is normally developed for diabetes and its antibiotic properties were discovered using machine learning method.
In the experiments, E. Coli developed resistance against ciprofloxacin but not against the Halicin.
Acinetobacter has gained resistance to at least 3 antibiotic classes, and due to their resistance to environmental conditions, they can maintain their vitality for a long time in the hospital environment.
In addition, their natural resistance to many antibiotics and their ability to develop resistance in a short time,gradually limits the antimicrobials that can be used in the treatment of infections they cause. Acinetobacter is not resistant to Halicin today.
If we consider the cells as a larger factory consisting of the chain work of small factories, the failure of an important function will affect the whole system.
When we examine the working principles of antibiotics, they basically do:
Unnecessary use of antibiotics is one of the most important factors affecting antibiotic resistance. Bacteria in a bacterial population are genetically different from each other, even if this changes are very small.
The unconscious use of antibiotics puts an evolutionary pressure on the population. If you are lucky all bacteria die, if you are not, the resistant ones will survive and you will have unintentionally performed artificial selection.
Apart from their chromosomes, bacteria have another genetic information called a plasmid. Generally, genes that enable resistance to develop evolve here, such as an enzyme that inactivates the antibiotic.
Resistance genes spread to the population as the cell divides vertically or horizontally by conjugation, viruses, etc. Also, viruses and bacteria have an advantage over larger creatures in the evolutionary arms race because they reproduce very quickly and thus achieve greater genetic diversity and ultimately function.
Gene expressions of bacteria exposed to Halicin were examined, and as a result, changes in protein production in movement and energy production mechanisms were observed.
While generating energy, cells benefit from the flow of potential energy from high to low, similar to hydroelectric power plants. It is protons, not water, flowing here.
Unlike the classical antibiotics, Halicin damages the bacteria’s ability to maintain the electrochemical potential between membranes. As a result, ATP cannot turn into motion energy and the bacteria remain inactive, more importantly, energy production stops and then the cell dies. Any complex system without energy is doomed to disintegration.