7.2 Dr. Ehrlich’s Magic Bullet Emerging Diseases Lecture 7: Antibiotics 7.1 Overview 7.2 Dr. Ehrlich’s Magic Bullet 7.3 Sulfa drugs 7.4 Antibiotics 7.5 Disambiguation

7.1: Overview: Disease Prevention Strategies Based on the Germ Theory Clean streets Sewers and plumbing An emphasis on hygiene for everyone (socialism of the microbe) Antiseptic surgical procedures Vaccines (later in 20th Century)

Another approach is to use chemicals as medicines to kill germs after they attack. A “cure” not a preventative Very useful when prevention methods fail.

Disease Cures??? According to the Germ Theory-killing the germs ought to work well How do you kill living germ cells without harming the patient?

Antiseptics such as Lister’s carbolic acid killed germs on surfaces but were too powerful to administer to a sick patient. By the start of the 20th Century the search was on for a chemical that could kills germs inside a living person without harm.

7.2: Paul Ehrlich and the “Magic Bullet” Salvarsan-Compound 606 Early antimicrobial chemical Introduced in 1910s Not 100% effective Long treatment: 1-2 years

Salvarsan was the first effective antimicrobial drug in Western medicine-so famous there was a movie about it.

Salvarsan was used to fight Syphilis Infections Infectious agent is Treponema pallidum a “spirochaete” Sexual transmission, may also be transmitted through cuts and scrapes Can cause skin infection called “yaws” Salvarsan was much better than earlier “cures” High fevers?

Syphilis was anAn Emerging Disease in the 1500s First European outbreak in 1494 Origins-a new version of an old disease? Or an entirely new disease? Highly fatal in 1500s The “Great Pox” The “French Disease” A New World disease brought back to the Old World by Columbus’ sailors???????

Syphilis has a variety of symptoms and forms Primary-large sore aka chancre Secondary-many possible symptoms including skin rash Latent-no symptoms but still infectious Tertiary-disease invades entire body including bones and brain Syphilis is called the Great Imitator because its symptoms resemble those of other diseases

Some symptoms and stages A serious problem for society

A serious problem because A serious problem because... An STD so very widely transmitted In the latent stage people thought they were cured and continued to be sexually active Can be transmitted from infected mother to baby at birth “Congenital” syphilis accounted for many institutionalized patients in 19th Century

7.3: Sulfa Drugs Later class of anti-microbial compounds Discovered in Germany 1935 Very effective but some side effects The “First Wonder Drug” Used against many microbes

Sulfa drugs were the second successful group of antimicrobial drugs Sulfa drugs were the second successful group of antimicrobial drugs. Saved many lives in World War II

7.4: Antibiotics- a new class of antimicrobial in the 1940s Penicillin-produced by a fungus “Discovered” in 1928 and investigated by Alexander Fleming Difficult to purify in quantity Not effective against all microbes Mass production an Allied effort in World War II Antibiotics are produced by a living organism to fight microbes

Antibiotics such as penicillin are different from Salvarsan and sulfa drugs. Antibiotics come from a living organism not a chemical factory. Salvarsan and sulfa drugs are artificial but antibiotics are natural in the sense that they are used in nature by one organism against another.

Streptomycin Second important antibiotic Effective against microbes that are not harmed by penicillin Waksman usually credited-1943 Used to treat tuberculosis

Antibiotics today Second or third-generation compounds: ampicillin, carbenicillin, methicillin, etc. Resistance is the problem today The widespread use of antibiotics selects resistant strains.

Most natural microbes are susceptible to and can be killed by antibiotics. But microbial populations are large And they always contain some pre-existing mutants that are resistant to antibiotics.

When antibiotics kill off the susceptible cells-only the resistant ones remain. This is an example of artificial selection.

Thus, hospitals, clinics, etc, (any place where antibiotics are used a lot) are great places to find resistant microorganisms.

Once a resistance gene is selected, microbes have many ways to share it among themselves by sharing pieces of DNA. This is called horizontal gene transfer. It allows the rapid spread of antibiotic resistance.

Sometimes the genes for many different types of antibiotic resistance travel on the same piece of DNA and get shared widely. Can lead to multi-drug resistant microorganisms.

7.5: Disambiguation Antibiotics work against living organisms such as bacteria. They are useless against non-living pathogens. (viruses and subviral pathogens) Antiviral compounds are used against viruses. Antimycotics are used against fungi.