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Photo of a variety of plants being sold by a street vendor.
For millennia, Chinese herbalists have used many different species of plants for the treatment of a wide variety of human ailments.
  • Give examples of how antimicrobials were used in ancient societies.

The first antimicrobial drugs

Societies relied on traditional medicine for thousands of years; however, the first half of the 20th century brought an era of strategic drug discovery. In the early 1900s, the German physician and scientist Paul Ehrlich (1854–1915) set out to discover or synthesize chemical compounds capable of killing infectious microbes without harming the patient. In 1909, after screening more than 600 arsenic-containing compounds, Ehrlich’s assistant Sahachiro Hata (1873–1938) found one such “magic bullet.” Compound 606 targeted the bacterium Treponema pallidum , the causative agent of syphilis. Compound 606 was found to successfully cure syphilis in rabbits and soon after was marketed under the name Salvarsan as a remedy for the disease in humans ( [link] ). Ehrlich’s innovative approach of systematically screening a wide variety of compounds remains a common strategy for the discovery of new antimicrobial agents even today.

Drawing of Paul Ehrlich in the lab.
Paul Ehrlich was influential in the discovery of Compound 606, an antimicrobial agent that proved to be an effective treatment for syphilis.

A few decades later, German scientists Josef Klarer , Fritz Mietzsch , and Gerhard Domagk discovered the antibacterial activity of a synthetic dye, prontosil , that could treat streptococcal and staphylococcal infections in mice. Domagk’s own daughter was one of the first human recipients of the drug, which completely cured her of a severe streptococcal infection that had resulted from a poke with an embroidery needle. Gerhard Domagk (1895–1964) was awarded the Nobel Prize in Medicine in 1939 for his work with prontosil and sulfanilamide , the active breakdown product of prontosil in the body. Sulfanilamide, the first synthetic antimicrobial created, served as the foundation for the chemical development of a family of sulfa drugs. A synthetic antimicrobial is a drug that is developed from a chemical not found in nature. The success of the sulfa drugs led to the discovery and production of additional important classes of synthetic antimicrobials, including the quinolines and oxazolidinones .

A few years before the discovery of prontosil, scientist Alexander Fleming (1881–1955) made his own accidental discovery that turned out to be monumental. In 1928, Fleming returned from holiday and examined some old plates of staphylococci in his research laboratory at St. Mary’s Hospital in London. He observed that contaminating mold growth (subsequently identified as a strain of Penicillium notatum ) inhibited staphylococcal growth on one plate. Fleming, therefore, is credited with the discovery of penicillin , the first natural antibiotic , ( [link] ). Further experimentation showed that penicillin from the mold was antibacterial against streptococci, meningococci, and Corynebacterium diphtheriae , the causative agent of diphtheria.

Fleming and his colleagues were credited with discovering and identifying penicillin, but its isolation and mass production were accomplished by a team of researchers at Oxford University under the direction of Howard Florey (1898–1968) and Ernst Chain (1906–1979) ( [link] ). In 1940, the research team purified penicillin and reported its success as an antimicrobial agent against streptococcal infections in mice. Their subsequent work with human subjects also showed penicillin to be very effective. Because of their important work, Fleming, Florey, and Chain were awarded the Nobel Prize in Physiology and Medicine in 1945.

In the early 1940s, scientist Dorothy Hodgkin (1910–1994), who studied crystallography at Oxford University, used X-rays to analyze the structure of a variety of natural products. In 1946, she determined the structure of penicillin, for which she was awarded the Nobel Prize in Chemistry in 1964. Once the structure was understood, scientists could modify it to produce a variety of semisynthetic penicillins. A semisynthetic antimicrobial is a chemically modified derivative of a natural antibiotic. The chemical modifications are generally designed to increase the range of bacteria targeted, increase stability, decrease toxicity, or confer other properties beneficial for treating infections.

Penicillin is only one example of a natural antibiotic. Also in the 1940s, Selman Waksman (1888–1973) ( [link] ), a prominent soil microbiologist at Rutgers University, led a research team that discovered several antimicrobials, including actinomycin , streptomycin , and neomycin . The discoveries of these antimicrobials stemmed from Waksman’s study of fungi and the Actinobacteria , including soil bacteria in the genus Streptomyces , known for their natural production of a wide variety of antimicrobials. His work earned him the Nobel Prize in Physiology and Medicine in 1952. The actinomycetes are the source of more than half of all natural antibiotics J. Berdy. “Bioactive Microbial Metabolites.” The Journal of Antibiotics 58 no. 1 (2005):1–26. and continue to serve as an excellent reservoir for the discovery of novel antimicrobial agents. Some researchers argue that we have not yet come close to tapping the full antimicrobial potential of this group. M. Baltz. “Antimicrobials from Actinomycetes: Back to the Future.” Microbe 2 no. 3 (2007):125–131.

a) Photo of Alexander Fleming. B) Photo of Howard Florey and Ernst Chain.
(a) Alexander Fleming was the first to discover a naturally produced antimicrobial, penicillin, in 1928. (b) Howard Florey and Ernst Chain discovered how to scale up penicillin production. Then they figured out how to purify it and showed its efficacy as an antimicrobial in animal and human trials in the early 1940s.
Photo of Selman Waksman in the lab.
Selman Waksman was the first to show the vast antimicrobial production capabilities of a group of soil bacteria, the actinomycetes.
  • Why is the soil a reservoir for antimicrobial resistance genes?

Key concepts and summary

  • Antimicrobial drugs produced by purposeful fermentation and/or contained in plants have been used as traditional medicines in many cultures for millennia.
  • The purposeful and systematic search for a chemical “magic bullet” that specifically target infectious microbes was initiated by Paul Ehrlich in the early 20th century.
  • The discovery of the natural antibiotic , penicillin, by Alexander Fleming in 1928 started the modern age of antimicrobial discovery and research.
  • Sulfanilamide, the first synthetic antimicrobial , was discovered by Gerhard Domagk and colleagues and is a breakdown product of the synthetic dye, prontosil.

Fill in the blank

The group of soil bacteria known for their ability to produce a wide variety of antimicrobials is called the ________.

actinomycetes

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Short answer

Where do antimicrobials come from naturally? Why?

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Why was Salvarsan considered to be a “magic bullet” for the treatment of syphilis?

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Questions & Answers

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What is the difference between TVC and Bioburden test
Mohamed
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Mohamed
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life arises from living matter or live organism.
Swami Reply
yes
sildra
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sildra
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Manya
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sildra
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Manya
eno
sildra
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sildra
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Manya
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Family kindly help me with this question? 1) Shortlist the configurative measurements of the following human anatomical ranges of÷ - Blood ( haemeglobin) in both male and female - Haematocytes in both male and female - Hepatocytes in both male and female - Lymphocyte / T. Lymphocytes in both male
Gifted
My names are Gift Mwale and am a Zambian. Kindly help me with this research which goes like this... 1) Shortlist the configurative measurements of the following human anatomical ranges of ÷ - Blood ( haemeglobin) in both male and female - Hepatocytes in both male and female - Haematocytes in both
Gifted
please what is the full meaning for TCDS
UDEME
from a single cell
Freedom
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Manya
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feven
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BELLO Reply
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Abdulkareem
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BELLO
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is unit of life
Kamaluddeen
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disease due to __________ abnormalities are termed primary immunodeficiencies
Tayee Reply
Some primary immunodeficiencies are due to a defect of a single cellular or humoral component of the immune system.
Prince
Examples of primary immunodeficiencies include: chronic granulomatous disease, X-linked agammaglobulinemia, selective IgA deficiency etc
Prince
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Emerald
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Cynthia Reply
alteration in genetic makeup
UDEME

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Source:  OpenStax, Microbiology. OpenStax CNX. Nov 01, 2016 Download for free at http://cnx.org/content/col12087/1.4
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