Bacteriophages – A Solution To Antibiotic Immunity
A Brief History Of Antibiotics And Antibiotic Immunity
In 1928, Alexander Fleming discovered the first antibiotic: Penicillin. After returning from holiday in early September to St. Mary’s hospital in London, Fleming began to sort through petri dishes he had left growing with various bacteria culture whilst he was away. Fleming noted that a dish containing Staphylococcus bacteria had a culture of mould (later identified as a strain of Penicillium Notatum) growing on the dish, and that an area clear of bacteria growth had formed around this patch of mould. Fleming concluded that the mould must have been producing something that inhibited bacteria growth 1.
After years of research, today we know that antibiotics are produced by various different fungi, and inhibit key processes bacteria need to replicate, such as cell wall synthesis and DNA replication 2. They are now used all over the world to treat numerous different diseases, with different strengths reserved for tougher infections. In countries such as the UK, antibiotics must be prescribed. In others, such as the USA, they can be bought directly off the shelves.
Antibiotic immunity was known about since the discovery of antibiotics. Alexander Fleming himself warned that the misuse of antibiotics could lead to the rise of superbugs, and advocated for the strict regulation of penicillin and alike. This was further supported by observations in 1940 made by Sir Edward Abraham and Sir Ernst Chain during WW2, where the first large scale use of penicillin took place, of an enzyme that broke down Penicillin 4.
Antibiotic immunity arises when a culture of bacteria is exposed to antibiotics for a long period of time. Since bacteria replicate so quickly, mutations which allow bacteria to survive in antibiotic environments become common, and allow the bacteria to thrive as there is no competition for space or food. Bacteria are also able to pass on their genetic code to others around them through a process called bacterial conjugation, so immunity genes can be passed to bacteria that were previously not immune 3.
Areas of high antibiotic concentration are where immunity is most likely to become present, such as in hospitals. Patients prescribed an antibiotic course and then not completing it is also responsible, and it is argued that places where antibiotics can be bought off of the shelves made the situation worse. Antibiotics were often used for only minor infections that the body could fight off normally, (such as the common cold), and patients would often not complete the course of antibiotics because they no longer had the symptoms, not realising that that didn’t mean that all of the infection had been cleared.
It is argued that the biggest responsibility of widespread antibiotic immunity is in the farming industry, where healthy livestock are fed antibiotics mixed in with feed to prevent disease spreading. Colistin is the strongest antibiotic and was only traditionally used as a last resort effort to clear an infection of a superbug resistant to all other strengths of antibiotic. However, in 2016 it was found that this antibiotic was regularly being used on livestock in China, and a gene had been found that was resistant to Colistin, meaning that there are now superbugs that are resistant to all antibiotics. The gene has been found in over 30 countries. In the USA, a patient was infected with e-Coli that carried the gene the same year 5. This widespread antibiotic immunity is rendering many antibiotics completely obsolete, which is a huge problem. Many figures in the scientific community worry that this could send humanity back to the dark ages unless something is done. It will mean that deaths from previously easily curable infections could significantly rise, and will also stop surgery from being possible, due to the antibiotics needed to prevent infection.
However, possible solutions have been found, one of which is looking particularly promising.
Bacteriophages, more commonly known simply as “Phages”, are a form of virus that are specialised so that they are only able to infect a certain species of bacteria. It is still disputed on whether or not viruses are alive or dead, since their only function is reproduction. The most common type of Phages consist of a spherical protein head (capsid), which contains genetic material, and a tail, which as “legs” used for attaching to receptors on a bacteria cell wall, and a syringe like structure used for injecting the genetic material of the phage into the host cell 6.
A Phage’s genetic material codes for the construction of the protein structures required to make more Phages. The reproduction of Phages happens during th Lytic cycle:
1. Attachment: The tail of the Phage binds to receptors on the wall of the bacteria cell.
2. Entry: The double helix DNA is injected from the capsid into the Bacteria’s cytoplasm.
3. DNA/Protein synthesis: The DNA of the Phage is mistakenly read by the bacteria, and codes for the construction of proteins that make up the Phage (for example, the capsid). The DNA of the Phage is also replicated.
4. Assembly: Proteins synthesised by the bacteria, and replicated Phage DNA, are brought together to create a new Phage (Hundreds are created).
5. Lysis: At a later stage, enzymes are produced that digest the cell wall. Water then enters the cell through the newly created holes (osmosis), and the cell bursts, releasing the Phages within.
This form of reproduction can prove to be devastating to bacteria, as one Phage produces hundreds more, which go on to infect and destroy other near by bacteria. 6