Stephanie Amatuzzo Katelynn Granger Kelly Beasley Marley Roberts Antibacterials

D.6.1 Outline the historical development of penicillins. D.6.2 Explain how penicillins work and discuss the effects of modifying the side- chain. D.6.3 Discuss and explain the importance of patient compliance and the effect of penicillin overprescription. D.8.3 Explain the importance of the beta- lactam ring action of penicillin.

D.6.1 Outline the historical development of penicillins; The background 1940: Penicillin is founded opened era of antibiotics Antibiotics: compounds produced by bacteria and fungi which are capable of killing, or inhibiting, competing microbial species Development of penicillin is seen as greatest advancement in therapeutics Combined efforts of United States and United Kingdom Actually discovered in UK Due to WWII USA mass produced the product

Before Penicillin… No effective treatment for infections such as pneumonia, gonorrhea, or rheumatic fever Ancient Egyptians had the practice of applying a poultice of moldy bread to infected wounds.

The Discovery Alexander Fleming, 1928 sort through petri dishes containing colonies of Staphylococcus, bacteria that cause boils, sore throats, and abscesses. He noticed something unusual on one dish. It was dotted with colonies, save for one area where a blob of mold was growing. The zone immediately around the mold - later identified as a rare strain of Penicillium notatum - was clear, as if the mold had secreted something that inhibited bacterial growth. isolated pure penicillin from the mold juice

Lab experiment to life saver Their work on the purification and chemistry of penicillin began in 1939 wartime conditions were beginning to make research especially difficult February 12, 1941: First taken by a human Healed a man within days having huge abscesses affecting his eyes, face, and lungs

The USA saves the day Britain not able to mass produces because of war US began mass producing penicillin Increased production Substituted lactose for sucrose Added corn-steep liquor to fermentation medium Exposed strand to UV light

D.6.2 Explain how penicillins work and discuss the effects of modifying the side- chain. How penicillin destroy bacteria: 1. Prevents cell wall formation so cell shape can't be maintained 2. Water enters the cells 3. The cells burst and the bacteria die.

There are two types of bacteria… Gram positive and gram negative. Gram positive bacteria have a simple cell wall. Gram negative bacteria have complex many layered cell walls. Some antibiotics are ineffective because it is difficult to penetrate the outer layer of gram negative bacteria.

Effects of Modifying the Side Chain The structure of penicillin contains An R group (side chain) A carboxylic acid group, and A beta- lactam ring Different types of penicillin vary in their R group (side chain). Modifying the R group changes the bacteria destroying ability of the penicillin, therefore the structure of penicillin affects its ability to work in different environments. Different R groups side chains changes its activity. R group Carboxylic acid group Beta- lactam ring

The First Penicillin was called Penicillin G. However it was deactivated by stomach acid so, the benzene side chain was modified to form the modern form of Penicillin V (regular broad spectrum antibiotic prescribed today), which is acid resistant, more soluble in water and is resistant to penicillinase. Penicillinase is an enzyme produced by bacteria that deactivates penicillin preventing it from destroying bacteria. Penicillin G Penicillin V

D.6.3 Discuss and explain the importance of patient compliance and the effect of penicillin over-prescription. :30

Broad vs. Narrow Spectrum Antibiotics Narrow spectrum antibiotics effective against certain types/strains bacteria leaving other unharmed. The specific bacteria is identified with a blood or urine test so the specific antibiotic can be identified and prescribed. Broad spectrum antibiotics effective against a wide range of types and strains of bacteria, including helpful/beneficial ones (major disadvantage). Blood/urine test not required. Can be brought over the counter. The destroyed bacteria may also be replaced with harmful strains of the same bacteria.

Patient Compliance Symptoms of a bacterial infection often disappear after a few days, so people may think that they are free from the infection In reality, the symptoms are gone, but the bacteria are still present in the body Stopping antibiotics before the medication runs out increases the number of antibiotic-resistant bacteria and decreases the effectiveness of the antibiotics This can lead to more severe illness or even hospitalization, depending on the type and strength of the bacteria.

Disadvantages of Over-prescription of Penicillins About 10% of the population experiences allergic reactions to penicillins (like fever, rash, shock, and/ or death) Overprescription can also have these results. Helpful bacteria in the alimentary canal can be wiped out by antibiotics and can be replaced by more harmful strains of the same bacteria. When antibiotics are used extensively, the few bacteria that survive pass on their resistance when they reproduce. This results in strains of the bacteria that are resistant to one or more antibiotics, such as some strains of tuberculosis, typhoid, and gonorrhea. Mutations in a bacterium can also cause antibiotic resistance, sometimes coupled with increased reproductive abilities.

Furthermore.. More research is needed to develop new antibiotics that will be effective on bacteria that are resistant to existing antibiotics Antibiotics should only be used when no other treatment can reduce a patient’s suffering or save their life. This does not always work, since antibiotics are often misused and abused in today’s society

Antibiotics in Animal Feedstock Antibiotics are used in animal feedstock as supplements to increase the growth of the animals and control the spread of disease They are used to eliminate pathogens that may be present in the feedstock and increase productivity This continuous, low-dose exposure to antibiotics stimulates the evolution and spread of drug-resistant bacteria The same antibiotics that are found in animal feedstock are used to treat bacterial infections in humans Therefore, these strains of bacteria can also affect humans.

D.8.3 Explain the importance of the beta- lactam ring action of penicillin. Beta- lactam ring The beta- lactam ring is a heroatomic ring structure consisting of one nitrogen and three carbons Square planar structure, bond angles of 90˚ The carbon atoms and the nitrogen would prefer tetrahedral angles of about 109˚ and the carbon double bonded to the oxygen would prefer an angle of 120˚. The angles of 90˚ therefore place the ring under chemical stress, which increases its chemical reactivity, opening the ring.

Effects of the Open Ring This open structure is able to covalently bond to the enzyme transpepidase which is responsible for the synthesis of the bacterial cell walls, thus blocking the action of the enzyme. The reaction of the penicillin with the enzyme is NOT reversible and thus it inhibits the synthesis and growth of bacteria in the cell wall. More specifically, it prevents the cross linking of the peptides; the bacteria burst without the linkage between the bacterial cell walls.