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history and modern development of antibiotics
Transcript of history and modern development of antibiotics
Timeline of antibiotic development
• Bacteria are unicellular prokaryotic microorganisms. Some bacteria are actually helpful to people by assisting in the digestion of food and producing vitamins.
• However, other bacteria are infectious and can produce toxins that damage tissue.
• Cell wall synthesis inhibitors
o Beta-lactamase inhibitors
• DNA synthesis Inhibitors
• RNA Synthesis Inhibitors
Classifications of Antibiotics
Antibiotics can be classified by their structure, chemistry, or mechanism of action
In this presentation we will see how antibiotics are classified based on their mechanisms
• Protein Synthesis Inhibitors
o Inhibit 30s subunit
o Inhibit 50s Subunit
Folic Acid Synthesis Inhibitors
Mycolic Acid Synthesis Inhibitors
treated scarlet fever, pneumonia, diphtheria, and meningitis.
Accidently discovered Staphylococcus aureus could be destroyed by mold Penicillium notatum.
He described the amount of inhibition and the effect of doubling the dilutions of his “inhibitor” yellow fluid, similar to our concept of minimum inhibitory concentration (MIC) and disk diffusion, and still extremely valuable today in the clinical setting.
Howard Florey + Ernst Chain
Mass production and distribution of penicillin in 1945
During WWII, Florey himself successfully tested the effects of penicillin on wounded soldiers
Fleming, Florey, and Chain shared 1945 Nobel Prize for their work on penicillin
The next goals were to identify the chemical structure with antibacterial activity. Later the isolation of 6-aminopenicillanic acid in 1959 made it possible to develop semisynthetic penicillins and the introduction of methicillin in 1960 and ampicillin in 1961.
Selman Waksman introduced the concept of antimicrobial activity, which describes the effect of small molecules made by a microbe, which antagonized the growth of other microbes.
The isolation of streptomycin from a culture of Spretomyces griseus was discovered to treat tuberculosis by Albert Schatz.
• Giuseppe Brotzu isolated a fungus Cephalosporium acremonium from sewer water. This discovery came about from observing that people from Cagliari, Italy had a lower population of people infected with typhoid fever.
Edward Abraham and Guy Newton collaborated with Brotzu to later produce different generations of Cephalosporins
o Ancient Egyptians, Chinese and central American Indians used molds and plants to treat infections and wounds
• They did not fully understand the connection of the antibacterial properties of mold.
• Anti-against bios-life “against life”
• An antibiotic is a type of medication that actually kills or prevents the growth of bacteria.
• An antibiotic is selective towards bacteria cells so that it doesn’t kill other cells in your body
What are antibiotics?
• Paul Ehrlich
Arsphenamine: used for the treatment of syphilis. Most used antimicrobial drug until the 1940s
Screening- the systematic testing of chemical compounds and their ability to modify their target, as now practiced in the pharmaceutical industry.
There was a splurge in the development of new antibiotics from the 1940s-1960s; however, no new class of antibiotics were discovered until the year 2000.
Most current antibiotics used today are synthetic derivatives of previous antibiotics introduced forty to fifty years ago.
Over time antibiotics have decreased in their effectiveness due to bacterial resistance.
Drug inactivation or modification
No binding or inhibition will take place because the bacteria can either change or camouflage the target site through mutations in genes.
Example: Alteration in penicillin-binding protein (PBPs) leading to reduced affinity of beta-lactam antibiotics (Methicillin-Resistant Staphylococcus aureus)
Alteration of metabolic pathway
Many drugs target certain parts of metabolic pathways by inactivating enzymes or sequestering substrates. Bacteria can use alternative metabolic pathways or find ways to uptake the necessary nutrients from the environment.
Example: Sulfonamide-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of folic acid and nucleic acids in bacteria inhibited by sulfonamides. Instead, like mammalian cells, they turn to utilizing preformed folic acid.
Reduced drug accumulation
Caused by reduced drug permeability or the ability of the bacteria to transport drugs out of the cell
Example: Increasing active efflux (pumping out) of the drugs across the cell surface.
The Future of Antibiotics
The need for a new class of antibiotic as a long-term solution to reducing the overall level of resistance.
The ability to test and identify patients who are carrying a milt-resistant strain is vital in achieving the full potential of this new class of antibiotic.
Continuing to create a next generation antibiotic rather than a new class can result in developing a high-level resistance in bacteria.
With this new class of antibiotics there needs to be prescription regulation in order to have a significant impact on antibiotic resistance.
Phage therapy: Bacteriophages or "phages" are viruses that invade bacterial cells and, in the case of lytic phages, disrupt bacterial metabolism and cause the bacterium to lyse. Phage therapy is the therapeutic use of lytic bacteriophage to treat pathogenic bacterial infections.
An antibiotic has lost its ability to kill or inhibit the growth of bacteria. Bacteria become resistant and can survive in the presence of antibiotics.
Enzymatic deactivation of the antibiotic.
Example: penicillin reistant bacteria like E.coli can produce beta-lactamases in order to inactivate the antibiotic. Through hydrolysis, the lactamase enzyme breaks open the beta-lactam ring structure, deactivating the antibiotic.