Antibiotics part 1 a game changer

Nov ,03 2016

Our battle with microbes began thousands years ago even before we first walked the Earth. As it might be beyond our imagination, the microbes ruled the Earth for a longer period of the time than humans exist as a species. And during this long time microbes have developed mechanism how to fight against each other in order to get better nutrients and space. These mechanisms often involved substances produced by one bacteria that either killed or inhibited the growth of other bacteria. And this fight have not yet ended because bacteria learned how to survive this attack by becoming tolerant or resistant to these products. Now, we call these products antibiotics and they involve all natural antibacterial substances produced by bacteria or fungi. Notably, all the antibiotics we use today are based on these natural products by some chemical modifications.

The discovery of antibiotics significantly revolutionized medicine in the 20th century and enabled procedures that we now take for granted. Consequently, antibiotics are more widely used than people might imagine and the world without antibiotics would be way different than the one we know today. Before the 20th century, the treatment of infections was primarily based on traditional medicine with recipes passed from generation to generation. Antimicrobial mixtures used for the treatment were described over 2000 years ago and many ancient cultures used specially selected mould and plant extracts to treat infections.

Typically during battles or war conflicts in the middle ages, if you have been wounded, you would most certainly have got a bacterial infection. If you were lucky, the infection was stopped and you survived. But more likely, the infection would spread and you would develop a gangrene (necrosis of tissues, organs or limbs) or a bacterial sepsis (a multiple organ failure due to the systemic bacterial infection) and ultimately you would die.

Antibiotics have changed this scenario completely. They made deadly infections such as tuberculosis treatable, and many other serious infections became minor or even neglected. The only treatment of tuberculosis before the antibiotics era was fresh air so you either lived or died depending on your immune system. Surgery that involves cutting the body open and thus possessing a massive risk of infection, became possible. Administration of antibiotics have enabled surgeons to perform operations that would have been deadly before. Cancer treatment by chemotherapy and radiotherapy often damages the patient’s immune system. And antibiotics help the body's own defence mechanisms to fight opportunistic infections. Organ transplant is another new chapter of medicine enabled thanks to antibiotics. Anyone who receives a transplanted organ has to also suppress their immune system, otherwise it would attack and destroy the organ. And antibiotics are used to protect the body from the attack from outside.

It all started in 1928, when Sir Alexander Fleming made one of the most significant observations in microbiology. Fleming was a well-known microbiologist already, for instance he discovered lysozyme, an antibacterial enzyme present in tears, saliva and mucus. However, lysozyme was only efficient against a small number of harmless bacteria, and thus it had a little therapeutic potential. Fleming did not give up though and kept searching for new antibacterial substances. During the summer 1928, Fleming was studying staphylococci when he went for holidays with his family and left his laboratory opened. When he came back, he discovered that on one of the bacterial plates a mould was growing and it created a bacteria-free zones (Fig. 1). The mould was later identified as Penicillium chrysogenum and the substance that it produced was named penicillin.

Penicillin seemed to have anti-bacterial effect on many Gram-positive bacteria, including the pathogens causing scarlet fever, pneumonia, meningitis and diphtheria. However, diseases caused by most Gram-negative bacteria, such as typhoid fever, were not affected except for Neisseria gonorrhoeae that causes gonorrhoea. Hence, penicillin was a real game changer.

Fig. 1: Diffusion method to test susceptibility of S. aureus to antibiotics – antibiotics diffuse from antibiotic-containing disks and inhibit growth of S. aureus, resulting in a zone of inhibition.

However, Fleming as a microbiologist was never able to produce penicillin for a mass treatment. The problem was that growing penicillium was quite tricky and it was even more difficult to isolate the substance in a quantity and purity that was required for a successful treatment. Finally, in 1940, Fleming abandoned penicillin. However, two chemists, Howard Florey and Ernst Boris Chain, took up researching after him and succeeded in the mass production. By 1944, they were able to produce enough penicillin to treat all the wounded soldiers within the allied forces during the World War II.

For their great contribution to medicine Fleming, Florey and Chain, were awarded the Nobel Prize in Physiology or Medicine in 1945 (Fig. 2). But Fleming as the true microbiologist already saw the weakness of antibiotics and he pointed that in his winner’s lecture speech: "It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body. The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant." Sadly, he was right and now we have to face a new challenge.

Fig. 2: Nobel laureates in 1945.