Dr. Domagk, Prontosil and Sulfa Antimicrobials

Prontosil, Sulfonamides and Sulfanalimide Drug Therapy History

Mar 24, 2009 Donald Reinhardt

The German dye industry made many, varied chemicals including dyes for textiles and cells. Domagk's studies of one dye that killed microbes resulted in a Nobel Prize.

Ehrlich's Salvarsan studies, reported in 1909, clearly proved that injected drugs containing arsenic could control and destroy trypanosomes in animals and syphilis in people. Ehrlich's notable achievements stimulated others to begin thinking about finding and discovering new and useful antimicrobial chemicals or drugs.

Like Ehrlich, Domagk had served in the German Army during WW I. He witnessed the untreatable ravages of dysentery, tetanus, typhus, gas gangrene and other serious infectious diseases. Encouraged by the effectiveness of Ehrlich's arsenic drug against the treponmes of syphilis, Domagk was motivated now as a medical doctor to seek chemical cures.

Ehrlich's Magic Bullet and Domagk's Critical Experiments

Ehrlich believed that antimicrobials and their target cells must have a certain fit. The "magic bullet" was simply the fit of the antimicrobial to the pathogen, not the host. That was critical.

Working in his lab, with a variety of chemicals, Domagk tested each chemical on:

agar plates inoculated with microbes.
mice and rabbits injected with pathogens.

Survival of test animals was particularly good when they were injected with prontosil. Streptococcus bacteria were evaluated and tested repeatedly. The patterns and conclusions emerged, prontosil was an effective antimicrobial.

A Special and Undesired Test for Domagk

Prontosil had not yet been tested in humans when a crisis emerged. Domagk's only daughter developed a severe streptococcal infection in her arm. Both arm and life were at risk. Domagk decided there was only one thing to do. He injected her with prontosil. She responded well. The diseased arm was restored to full health. Rather than shout this before the whole world, Domagk remained patient until other human tests were done over the next few years.

Sulfa Drugs PABA Folic Acid: Biochemical Decoys and Enzyme Competitive Inhibition

The red dye "prontosil rubrum" is modified in the host to become a true sulfonamide antibiotic. Click on the figure at the bottom to enlarge and to see what a basic sulfa drug looks like compared to PABA The sulfa drug mimics or looks like the common natural substance called PABA. Here are some things to remember:

Para-aminobenzoic acid (PABA) is an important precursor to folic acid, a critical vitamin and growth factor needed for carbon transfers inside all bacterial and animal cells.
Many bacteria cannot use a host's folic acid because the molecule is too big. Instead they have an enzyme (protein catalyst) that transports the PABA across their outer wall and membrane and into the bacterium's cytoplasm.
Once inside PABA can be converted to the larger folic acid molecule. Now, with folic acid they can live; without folic acid these cells simply starve and die.
Since the sulfa drug looks like PABA, the enzyme often grabs the sulfa drug, not the PABA.
Big mistake for that enzyme! The enzyme becomes inactive. It has been fooled and took the decoy like a fish swallowing a plastic worm which, in this case, seals the fish's mouth shut.

It is possible to fool and trick microbial enzymes into accepting some molecules that seem proper to them for nutrition and metabolism. If that enzyme grabs onto the decoy, it combines, locks up and cannot release. Sulfa drugs do this to enzymes, they cannot function, and folic acid is not made. The bacterial cell starves to death. Good for the host, bad for the bacteria!

Dr. Domagk developed two successful other drugs to inactivate the bacterium of tuberculosis.Toward the end of his career he studied aspects of chemotherapy for cancer. He considered that a most important goal of science.

Thanks to Dr Domagk, chemists, and microbiologists, another positive score was added on the card for the human team in their battle against team "Pathogenic Microbes". It is a very long and difficult struggle, as past and recent history shows.

Sources and ResourcesThe Nobel Prize Winner in Medicine or Physiology.1939. Nobel Foundation

The copyright of the article Dr. Domagk, Prontosil and Sulfa Antimicrobials in Microbiology is owned by Donald Reinhardt. Permission to republish Dr. Domagk, Prontosil and Sulfa Antimicrobials in print or online must be granted by the author in writing.

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Dr. Gerhard Domag	PABA and Sulfonamide Compared