Possibly the most concerning thing about the increasing ineffectiveness of certain antibiotics against bacteria, is the realisation that antibiotics as a whole are a relatively recent development in medical science. The earliest antibiotics were developed less than 100 years ago, which is an incredibly recent period in the history of humanity. In this article I wish to give a brief background about the history of antibiotics, so here we go.
The Early Days
I want to begin by acknowledging that the first instances of antibiotics being used may have been unintentional or accidental, there are records as far back as the ancient Egyptians using mould and other plants to treat infections and illnesses. As ancient societies had no knowledge of microscopic pathogens these treatments can only be seen as coincidental, trial and error medications.
It wouldn’t be until the 1660’s that bacteria would be first observed directly and later still in the 1850’s when Jon Snow, Louis Pasteur and Robert Koch developed and popularised germ theory that widespread acceptance of the existence of bacteria would occur.
Before antibiotics the fight against bacteria was primarily carried out through prevention of illness and increased sanitation. Once it was understood that microscopic organisms were responsible for spreading illness and disease, and these bacteria conglomerate in unsanitary areas, it became the mission of individuals such as Jon Snow and Florence Nightingale to prevent bacterial infections by promoting sanitation and cleanliness.
The breakthrough came from Sir Alexander Fleming; Fleming a Scottish biologist began his path to discovering antibiotics in 1921 by discovering the antiseptic enzyme ‘lysozyme’ which could kill minor groups of bacteria, but was not strong enough to fight infections. In 1928 however while experimenting at St Mary’s Hosptial in London, Fleming (a notoriously untidy lab technician) returned from a two week holiday to find mould growing over his bacterial cultures, he noticed that one agar plate in particular containing the bacterium Staphylococcus, contained dead bacteria. Fleming identified the mould as Penicillium Notatum and began experimenting, he discovered that he could squeeze ‘mould juice’ from the mould which would kill the bacteria even after being diluted up to 800 times, it was this mould juice that Fleming would name Penicillin after the mould it came from. Sir Alexander Fleming was knighted in 1944 and given the Nobel prize for medicine in 1945 for his monumental discoveries.
Researchers in Europe and the United States began replicating Fleming’s experiments and mass producing Penicillin, soon pharmaceutical companies began selling it over the counter without prescription. It was in these early days that the first instances of antibiotic resistance occurred. Penicillin was marketed as a miracle drug and the public was uninformed as to how it worked, subsequently the drug was used for a variety of illnesses and maladies not associated with bacteria; strains of resistant Staphylococcus Aureus began appearing by the early 1940’s, the pharmaceutical industry began its search for new, more powerful antibiotics.
Post Penicillin Major Antibiotics
Table 1: Timeline of the discovery and introduction of antibiotics
|Antibiotic class; example||Year of discovery||Year of introduction||Year resistance observed||Mechanism of action||Activity or target species|
|Sulfadrugs; prontosil||1932||1936||1942||Inhibition of dihydropteroate synthetase||Gram-positive bacteria|
|β-lactams; penicillin||1928||1938||1945||Inhibition of cell wall biosynthesis||Broad-spectrum activity|
|Aminoglycosides; streptomycin||1943||1946||1946||Binding of 30S ribosomal subunit||Broad-spectrum activity|
|Chloramphenicols; chloramphenicol||1946||1948||1950||Binding of 50S ribosomal subunit||Broad-spectrum activity|
|Macrolides; erythromycin||1948||1951||1955||Binding of 50S ribosomal subunit||Broad-spectrum activity|
|Tetracyclines; chlortetracycline||1944||1952||1950||Binding of 30S ribosomal subunit||Broad-spectrum activity|
|Rifamycins; rifampicin||1957||1958||1962||Binding of RNA polymerase β-subunit||Gram-positive bacteria|
|Glycopeptides; vancomycin||1953||1958||1960||Inhibition of cell wall biosynthesis||Gram-positive bacteria|
|Quinolones; ciprofloxacin||1961||1968||1968||Inhibition of DNA synthesis||Broad-spectrum activity|
|Streptogramins; streptogramin B||1963||1998||1964||Binding of 50S ribosomal subunit||Gram-positive bacteria|
|Oxazolidinones; linezolid||1955||2000||2001||Binding of 50S ribosomal subunit||Gram-positive bacteria|
|Lipopetides; daptomycin||1986||2003||1987||Depolarization of cell membrane||Gram-positive bacteria|
|Fidaxomicin (targetingClostridium difficile)||1948||2011||1977||Inhibition of RNA polymerase||Gram-positive bacteria|
|Diarylquinolines; bedaquiline||1997||2012||2006||Inhibition of F1FO-ATPase||Narrow-spectrum activity (Mycobacterium tuberculosis)|
Source: Lewis, K 2013, ‘Platforms for antibiotic discovery’, Nature Reviews Drug Discovery, vol. 12, pp 371-387
In our next post which you can read here, we ask the question: Where are the new antibiotics?
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