The history of antibiotics

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Introduction
What are antibiotics?
History of Antibiotics
Beginning of the era of antibiotics
First clinical use of antibiotics
The Golden Age of Antibiotic Discovery
Developments in antibiotic discovery
References
Further reading


Antibiotics are medicines used to treat bacterial infections. Traces of antibiotics have been found in ancient human skeletons dating from 350 to 550 CE. In ancient Egyptian times, molds and plant extracts were used to treat infections. However, until the 19e century, it was not known that these infections were caused by microbes, in particular bacteria.

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What are antibiotics?

Antibiotics treat bacterial infections by killing bacteria or inhibiting bacterial growth inside the body. Antibiotics can be given orally (tablets, capsules, liquids), topically (cream, ointment, spray) or intravenously.

Antibiotics are not routinely prescribed for mild infections, lung infections, ear infections, and sore throats. Also, antibiotics do not treat viral infections, including colds and flu. Frequent or inappropriate use of antibiotics can lead to antibiotic resistance. In the United States, approximately 2 million infections are caused by antibiotic-resistant bacteria each year, resulting in 23,000 deaths.

History of Antibiotics

Before the discovery of antibiotics, infectious diseases were one of the main causes of morbidity and mortality in humans. Before the modern era of antibiotics began (more than 2000 years ago), microbes that produce antibiotics were used as interventions to treat infectious diseases in Serbia, China, Greece and Egypt. The Eber Papyrus, an Egyptian medical papyrus dated to 1550 BC. AD, is the oldest document describing the use of moldy bread and medicinal soils in the treatment of infections. Similarly, traces of tetracycline, an antibody with chelating effects, have been found in human bones collected in the oasis of Dakhleh, Egypt.

Phylogenetic reconstruction analysis has identified the persistent presence of several antibiotic resistance genes since ancient times. Phylogenetic analysis of β-lactamase and housekeeping genes revealed that these genes are highly conserved in Klebsiella oxytoca and have been evolving in the host for over 100 million years. Similarly, analysis of metagenomic clones obtained from 10,000-year-old ocean samples revealed that β-lactamase diversity is primarily associated with ancient evolution.

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Beginning of the era of antibiotics

The beginning of the modern antibiotic era can be marked by the discovery of a synthetic prodrug salvarsan and neosalvarsan by Paul Ehrlich in 1910 to treat Treponema pallidum, a spirochete bacterium that causes syphilis, a sexually transmitted disease. Inspired by his own discovery of dyes that specifically stain bacterial cells, Paul Ehrlich began screening a panel of synthetic drugs and later identified salvarsan.

Later, salvarsan was gradually replaced by a sulfonamide prodrug prontosil, which was discovered by bacteriologist Gerhard Domagk. Although sulfonamides are still used clinically as broad-spectrum antibiotics, the widespread use of these drugs was gradually replaced by the discovery of penicillin by Alexander Fleming in 1928. Fleming isolated and purified penicillin from a mushroom. Penicillium notatum who had accidentally contaminated a culture plate of Staphylococcus bacteria.

Later, the large-scale purification of penicillin was carried out by a team of Oxford scientists (Howard Florey, Ernst Chain and Norman Heatley), who aided in the mass production and distribution of penicillin in 1945. same year, Alexander Fleming along with Howard Florey and Ernst Chain received the Nobel Prize in Medicine “for the discovery of penicillin and its curative effect in various infectious diseases.”

First clinical use of antibiotics

Pyocyanase, an extract of Pseudomonas aeruginosawas the first antibiotic used in a hospital to treat hundreds of patients in the 1890s. Pyocyanase, discovered by Emmerich and Löw, was found to be effective against a variety of pathogens and was used well into the 1990s. 1910. Although initially thought to be an enzyme, pyocyanase might be a combination of pyocyanin, quorum-sensitive phenazine, and 2-alkyl-4-hydroxy-quinolones.

Appropriate use of antibiotics

The Golden Age of Antibiotic Discovery

Systemic evaluation of microbes and their ability to produce antimicrobial compounds was first initiated by Selman Waksman in the 1930s. He defined an antibiotic as “a compound made by a microbe to destroy other microbes” and discovered several antibiotics from soil-dwelling filamentous actinomycetes, including neomycin and streptomycin (antibiotics against tuberculosis).

The period between the 1940s and the 1960s has been considered the golden age of antibiotic discovery. The majority of antibiotics discovered during this period are still in clinical use today. However, a marked drop in their efficacy has been observed over time due to antibiotic resistance.

A sharp decline in the rate of antibiotic discovery after the 1970s, coupled with overuse of existing antibiotics, is the main cause of antibiotic resistance. A few antibiotics currently under investigation are synthetic antibiotics or derivatives of known classes of antibiotics. This calls for an urgent need to discover new classes of antibiotics to treat multidrug-resistant bacterial infections.

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Developments in antibiotic discovery

New classes of antibiotics are primarily identified by large-scale screening of antibiotic-producing soil organisms. The road to antibiotic discovery has been rejuvenated by the identification of new organisms in underexplored environments. Moreover, the development of new techniques for exploring the genome and expressing heterologous pathways has accelerated the discovery of new antibiotics.

The actinomycete genus Salinospora isolated from the marine environment has been identified as a good source of structurally novel antibiotics, including salinosporamide A, currently in a phase III clinical trial for the treatment of glioblastoma.

References

Further reading

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