Before resistance to antibiotics was noticed, the use of antibiotics had to become wide spread.

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Before resistance to antibiotics was noticed, the use of antibiotics had to become wide spread. Antibiotics are used to treat many bacterial disorders. They do so by selectively affecting the bacteria while leaving the human cells alone. This is an important feature that antibiotics must possess, because they would do little good if they killed the patient's cells along with the bacteria. Antibiotics have many different mechanisms of attack on the bacterial cells. In order to understand the resistance by the bacteria, the mechanism of attack from the antibiotic must first be understood.

Penicillin was the first antibiotic discovered in 1929. It was isolated from Penicillium notatum, a fungus. Penicillan is categorized as a β -lactam because of the β -lactam ring that is present in its chemical structure. It became commercially available in 1941 and was eventually isolated from P. chrysogenum since a better yield could be obtained. The first drug to become commercially available was prontosil and was used to fight murine streptococcal infection. A wave of antibiotic drugs with different mechanisms of attack against bacterial strains followed these two first antibiotics.

Penicillin stops bacterial cells reproduction by inhibiting the synthesis of a new cell wall, which is essential for the survival of the bacteria. Penicillin, as well as other β -lactams, inhibits the enzyme which places essential cross-links between the individual polymer strings of the cell wall. It does this specifically by using the β -lactam ring to irreversibly block the active site of the enzyme which catalyzes the reation, transpeptidase. This inhibition allows the bacteria to newly synthesize a cell wall and to elongate, but not divide. This is due to the lack of cross-linking which causes weak areas in the cell wall. These weak areas cause the bacteria to rupture. To see a movie of how penicillin works click .

An important antibiotic class are the sulphonamides. The first sulphonamide discovered was prontosil which was found to be converted into sulphanilamide in vivo. Both of these compounds were found to have antibacterial activites and lead to the discovery of other drugs. Several other sulphaniamide antibiotics were synthesized by substituting the end groups with different chemical substituents. Sulphonamides were the first man-made drugs to be used commercially.

Sulphonamides are specific to bacteria because of their mode of action. They inhibit the biosynthesis of folic acid, which does not occur in mammalian cells. The sulphonamides compete with p-aminobenxoic acid that is incorporated into terahydropteroic acid, an essential step in the pathway for the synthesis of folic acid and therefore inhibits the pathway. Sulphonamides are only active against Gram-positive bacteria, but have been used successfully to treat pneumonia, osteomyelitis, furuncle, carbuncle and puerperal infections.

Another important class of antibiotic chemicals are the quinolones. The first quinolone drug produced within the USA was nalidixic acid, followed by piromidic acid and pipemidic acid. One major breakthrough was to introduce the flourine atom into the quinolone molecule. This produced several new antibiotics and another class was formed, the fluoroquinolones. Different halogen substituents were placed into the same postition as the flourine. Each showed differences in their effectiveness of antibacterial activity against Escherichia coli, the most effective being fluorine and chlorine. Other compounds were also added to the ring structure which enhanced antibacterial activity. They included things such as piperazine, methylpiperazine, or a cyclopropyl group, to name a few. The fluoroquinolones mode of action was deduced to be caused from the inhibition of DNA synthesis. This differed from the penicillan mode of attack, which was to cause the cell to elongate and then inhibit the synthesis of the septa needed to separate the nuclei that form.

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Penicillin Terms

Alexander Fleming: Person often credited with the discovery of penicillin and its properties. For this discovery, he was knighted in 1943 and was one of three scientists to receive the 1945 Nobel Prize, in physiology and medicine. The other scientists were Howard Florey and Ernst Chain.

Antibiotic: A chemical substance that is used in the treatment of bacterial infectious diseases and has the ability to either kill or inhibit the growth of having the capacity in dilute solutions to either kill or inhibit the growth of certain harmful microorganisms.

Chain, Ernst: One of the main scientists who worked ...

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