Introduction to Antibiotics

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What are Antibiotics?

Chemical compounds used to treat infeections caused primarily by bacteria; they should be sufficiently non-toxic to be given to the infected host

Supplements the body's natural defenses to bacterial infections by killing or inhibiting bacteria

Classification

Natural antibiotics: 'true antibiotics' produced naturally by fungi or bacteria to selectively inhibit the growth of others (penicillin)

Semi-synthetic antibiotics: chemically modified natural antibiotics (Ampicillin)

Totally synthetic antibiotics: manufactured (trimethoprim)

Antibioticsa are clustered into Antimicrobial or chemotherapeutic agents

Further Classification:

Bactericidal(kill) or bacteriostatic(inhibit)

Narrow spectrum (limited) or Broad Spectrum (range)

Target site (selective toxicity)

Development of Chemotherapy

Selective Toxicity: exploit differences between structure and metabolism of infecting microorganisms and host cell. This is achievable in prokaryotes vs eukaryotes.

Procaryotes vs Eukaryotes:

Protective Outer layer: yes (cell wall) vs No

Ribosomes: Small (70s) vs Large (80s)

Nucleus: Free DNA vs membrane bound nucleus

Metabolism: variety of pathways vs common pathways

Discovery of Antibiotics

1928: Alexander Flemming accidentally dicovered penicillin

1939-1940 Howard Florey and Ernst Chain purified penicillin from penicillium notatum

1944: Selman Waksman discovered streptomycin produced by streptomyces griseus

1953: Microorganisms producing Chloramphenicol Tetracycline and Neomycin were isolated

Beta-lactam Antibiotics (bacterialcidal)

All have the beta lactam ring in their structure and the same mode of action. They inhibit peptidoglycan synthesis in bacteria; inhibit TRANSPEPTIDASE enzymes which affects final cross linking.

Transpeptidase catalyse the final stages of the peptidoglycan formation. Penicillin competatively inhibits D-alanyl D-alanine as it has a very similar structure, so transpeptidase binds to penicillin as it has a higher affinity. Inhibits the transpeptidase so pentaglycine cross link doesn't form. IRREVERSIBLE

Clinical usage of beta-lactam antibiotics

Tonsillitis

Pneumonia

STIs

UTI

Skin and tissue infections

Antibiotic Resistance

The abiltiy of a microorganism to withstand inhibition or killing by an antibiotic

"Some men are born great, some acheive greatness and some have greatness thrust upon them."

"Born great": natural resistance Mycobacterim tuberculosis lack a peptidoglycan cell wall so are naturally resistant to beta lactams.

"Achieve greatness": Genetic mutation caused spontaneously or after exposure to chemicals (relativly rare events) to produce a new population which is resistant to antibiotic

"Have greatness thrust upon them": Transfer of Resistance genes by:

Transformation: released DNA is taken up by another cell

Conjugation: Plasmid divided in two and passes one copy to another cell

Transduction: bacteriophage incorporates part of bacterial genome into its DNA, leaves and infects another cell with the new DNA

Antibiotic sensitivity testing

Determine whether bacteria are sensitive or resistant to different antibiotics inorder ti treat the infection and prevent bacterial resistance.

Diffuision: Disk diffusion Assay

Advantages: simple, inexpensice and screen lots of antibiotics.

Disadvantages:Qualitative but no information on antibiotic concentration

Dilution: Minimum inhibitory/bactericidal concentration:

Advantages: greater accuracy than agar disk diffusion. Quanititave provides information that can be used to modify treatment regimes.

Disadvantage: more expensive and labour intensive

MIC: lowest concentration of antibiotic needed to inhibit visable growth in broth

MBC: lowest concentration of an antibiotic needed to kill 99.9% of orignial bioload