Update on Antimicrobial Agents (Cairo University Lecture) PDF

Ahmed Sherif Attia, Ph.D. Update on Professor of Microbiology & Immunology antimicrobial agents Faculty of Pharmacy, Cairo University, Cairo, Egypt 1  Introduction Historical background...

Ahmed Sherif Attia, Ph.D. Update on Professor of Microbiology & Immunology antimicrobial agents Faculty of Pharmacy, Cairo University, Cairo, Egypt 1  Introduction Historical background Outline Mechanisms of action The post-antibiotic era 2  The Enemies (causative agents of infectious diseases) https://ib.bioninja.com.au/standard-level/topic-6-human-physiology/63-defence-against-infectio/pathogens.html 3  4 https://www.hse.ie/eng/services/list/2/gp/antibiotic-prescribing/antibicrobial-stewardship-audit-tools/  Chemical analysis of the bones of ancient Sudanese Nubians who lived nearly 2000 years ago shows they were ingesting the antibiotic tetracycline on a regular basis, likely from a special brew of beer. https://www.wired.com/2010/09/antibiotic-beer/ https://www.science.org/doi/10.1126/science.7001623 5 https://www.istockphoto.com/photo/once-upon-a-time-motivational-inspirational-quotes-gm1145940945-308607608  Carbolic acid used by Lister for killing microbes that could be Joseph Lister’s introduced during surgery is very good for killing them on surfaces. Antiseptic However, they were very harsh to be given to sick patients. Revolution Then the journey to find drugs that can kill microbes INSIDE the host without harming him started https://wellcomecollection.org/works/v4uj3nbe/items 6 https://daily.jstor.org/joseph-lister-antiseptic-revolution/ Paul Ehrlich- “Magic Bullet” - 1909 The term ‘magic bullet’ once just meant a targeted drug Salvarsan was the first effective antimicrobial drug in Western medicine Used to treat syphilis though not 100% effective and required long treatment (1-2 years) Nobel Prize winner honnered by being portraited on the 200-Deutsche Mark note https://www.filmaffinity.com/en/movieimage.php?imageId=413757156 So famous there was a movie about 7 https://cosmosmagazine.com/health/medicine/paul-ehrlichs-magic-bullet/ The First Miracle Drug “Sulpha Drugs” 1935 Discovered in 1935 by Gerehard Domagk “Germany”. The were used to treat many infections. They revolutionized medicine and saved thousands of lives especially in World War II. 8  9 http://melbourneblogger.blogspot.com/2019/05/the-true-story-of-penicillin-fleming.html National World War II museum https://bodyhorrors.wordpress.com/2012/12/06/a-moldy-cantaloupe/ 10 https://brian.carnell.com/articles/2021/world-war-ii-propaganda-poster-penicillin-saves-soldiers-liv What are antibiotics? Antibiotics are medicines that fight bacterial infections in people and animals. They work by killing the bacteria or by making it hard for the bacteria to grow and multiply. https://medlineplus.gov/antibiotics.html https://www.1mg.com/articles/know-your-medicines-antibiotics/ 11 Classes of antibiotics according to the origin 1- Natural They are derived from fungal sources and bacteria develop resistance faster to the natural antimicrobials as they already exposed to these compounds in nature. They are more toxic than other https://onlinelibrary.wiley.com/doi/10.1002/med.20154 type of antibiotics. Examples: Streptomycin, tetracycline and penicillins. 12  2- Semi-synthetic antibiotic: Part of the molecule is produced from a Classes of microorganism then the product is further modified by a chemical process antibiotics They are used to decrease toxicity and according to the increase effectiveness. Example: Many penicillins derivatives and origin cephalosporins 13 Classes of antibiotics according to the origin 3- Artificial or synthetic antibiotic: These drugs prepared in laboratory by chemical reactions. They have high effectiveness and less toxicity compared to other antibiotics. Example: Quinolones https://www.sigmaaldrich.com/EG/en/applications/chemistry-and-synthesis/synthetic- 14 methods/organic-reaction-toolbox  The evolution of antibiotics 15 https://doi.org/10.1016/j.mib.2019.10.008 The antibiotic discovery void 16  17 How do antibiotics work? https://www.istockphoto.com/search/2/image?mediatype=illustration&phrase=mechanism+of+action  1- Inhibition of cell wall synthesis (transpeptidase) β-lactam antibiotics inhibit the transpeptidase enzyme that catalyze the crosslinking of the amino acid side chains of NAM Goodman and Gilman’s The Pharmacological Basis of Therapeutics  1- Inhibition of cell wall synthesis (transglycosylase) Glycopeptides such as vancomycin inhibit the polymerization or transglycosylase reaction by binding to the d-alanyl-d-alanine terminus of the cell wall precursor unit attached to its lipid carrier and blocks linkage to the glycopeptide polymer. Goodman and Gilman’s The Pharmacological Basis of Therapeutics  2. Blocking protein synthesis (30S binders) Goodman and Gilman’s The Pharmacological Basis of Therapeutics  2. Blocking protein synthesis (30S binders) Tetracyclines bind to the 30S subunit, block tRNA binding to the A site, and thereby inhibit protein synthesis Goodman and Gilman’s The Pharmacological Basis of Therapeutics  2. Blocking protein synthesis (50S binders) Chloramphenicol binds to the 50S ribosomal subunit at the peptidyl transferase site, inhibiting transpeptidation Goodman and Gilman’s The Pharmacological Basis of Therapeutics  2. Blocking protein synthesis (50S binders) Macrolides are bacteriostatic agents that inhibit protein synthesis by binding reversibly to the 50S ribosomal subunits. Erythromycin appears to inhibit the translocation step such that the nascent peptide chain temporarily residing at the A site fails to move to the P, or donor, site. Goodman and Gilman’s The Pharmacological Basis of Therapeutics  3. Blocking nucleic acids synthesis (DNA) Nature Reviews Microbiology volume 8, pages423–435 (2010)  3. Blocking nucleic acids synthesis (RNA) https://www.internationaltextbookofleprosy.org/chapter/anti-leprosy-drugs-modes-action-and-mechanisms-resistance-mycobacterium-leprae  4- Injury to plasma membrane Cationic polymyxins bind to the negatively charged components of lipopolysaccharides and disrupts the outer membranes of Gram-negative bacteria https://doi.org/10.3390/membranes10080181 5- Anti-metabolites 27 What is common among these Mechanisms? They target essential processes..!!!....YET UNIQUE 28  Selective pressure leads to RESISTANCE https://genetics-evolution.weebly.com/selection-pressure.html 30