MEDCHEM E CHEMBIO Lectures_I

• Microorganisms


  Microscopic or sub-microscopic organisms, too small to be seen by the unaided human eye
• Microorganisms were first observed by Anton van Leeuwenhoek in 1675 using a microscope of his own design
• Bacteria

  A group of unicellular microorganisms, typically a few micrometres in length, that do not contain a nucleus (prokaryotes) and reproduce very quickly under the right circumstances
• Bacterial shapes


  • Bacillus (rod)
  • Coccus (spherical)
  • Spirillum (spiral)
  • Spirochaete (corkscrew)
  • Vibrios (comma)

  
• Escherichia coli (E. coli)


  A bacterium that lives in the lower intestine of warm-blooded animals and is used in modern biotechnology to store DNA sequences from other organisms and produce foreign proteins

  
• E. coli in the lab


  • Best growth temperature is 37°C, easy to "feed", can double every 20 minutes under ideal conditions, can grow with or without oxygen
• Fungi


  Eukaryotic organisms that lack chlorophyll and vascular tissue, ranging from single cells to branched filamentous hyphae that often produce specialized fruiting bodies
• Hypha

  Long, branching filamentous structure of a fungus, the main mode of vegetative growth, collectively called a mycelium
• Fungi in research


  • Important model research organisms, used to elucidate molecular events, prove the "one gene, one enzyme" hypothesis
• Viruses


  Minute infectious agents that lack independent metabolism and can only replicate within a living host cell, consisting of nucleic acid (DNA or RNA) and a protein shell

  
• Infection


  The detrimental colonization of a host organism by a foreign species (pathogen) that seeks to utilize the host's resources to multiply
• Infections are potentially so serious for humans that there is a specific branch of medicine dedicated to the study and treatment of them: infectious diseases
• Antibiotics


  Chemotherapeutic or antimicrobial agents with activity against microorganisms, originally substances produced by one microorganism that inhibit the growth of another
• Bacteriostatic and bactericidal antibiotics

  Bacteriostatic antibiotics stop bacteria from multiplying, bactericidal antibiotics kill bacteria
• Antibiotic

  Any chemotherapeutic agent or antimicrobial agent with activity against micro-organisms
• Antibiotics DO NOT kill viruses and the only scope they may have when used in a viral infection is to prevent the development of secondary bacterial infections
• Originally, an antibiotic


  A substance produced by one microorganism that selectively inhibited the growth of another
• Alexander Fleming discovered penicillin


  1928
• Bactericidal


  Antibiotics that kill bacteria, eg penicillins
• Bacteriostatic

  Antibiotics that just stop bacteria from multiplying
• Broad-spectrum antibiotics


  • Can be effective on different kinds of micro-organisms, for example they can be used for both Gram-positive and Gram-negative bacteria
• Narrow-spectrum antibiotics


  • Effective against only specific families of bacteria (for example staphylococci)
• Mechanisms of action of antibiotics

  • Interferes with Protein Synthesis
  • Interferes with DNA Synthesis
  • Interferes with Cell Wall Synthesis
  • Interferes with Cell Membrane Permeability
  • Inhibits an Enzyme
  • Modifies Membranes
• Gram staining


  1. Fixation of clinical materials to the surface of the microscope slide

  2. Addition of iodine solution to form a crystal violet iodine complex

  3. Application of organic solvents to extract the blue dye complex from the lipid-rich, thin walled gram negative bacteria

  4. Application of counter stain (safranin) to stain the decolorized gram-negative cells red/pink
• Penicillins


  Interfere with the biosynthesis of the bacterial cell wall, resulting in the death of the pathogen due to osmotic pressure
• Chloramphenicol


  Inhibits bacterial protein synthesis, has a very broad spectrum of activity: it is active against Gram-positive bacteria, Gram-negative bacteria and anaerobes
• Streptomycin


  Kills microbes by inhibiting protein synthesis and hurting cell membranes, binds to the rRNA of the small subunit of bacterial ribosome
• Aminoglycosides


  Contain as a portion of the molecule an amino-modified glycoside (sugar bound to another functional group via a glycosidic bond)
• Antibiotic resistance

  1. Can be acquired via natural selection acting upon random mutation

  2. Can be acquired via a donor cell's plasmid (circular unit of DNA), which has a resistance gene

  3. Bacterial cells can also acquire segments of DNA released from dead cells
• Aminoglycoside-modifying enzymes


  Catalyze the covalent modification of specific amino or hydroxyl functions, leading to a chemically modified drug which binds poorly to ribosomes
• Sometimes it is sufficient to synthesise a slightly different molecule to re-establish activity against antibiotic resistant bacteria
• Antiviral drugs

  A class of medication used specifically for treating viral infections, they are relatively harmless to the host
• Antibiotics cannot kill viruses because bacteria and viruses have different mechanisms and machinery to survive and replicate
• Vaccines


  Stimulate the immune system to produce antibodies, which then go out and "recognize" the virus to inactivate it
• Acyclovir


  A guanine analogue antiviral drug used for the treatment of herpes simplex virus infections, it is activated by viral thymidine kinase. the final product, acyclovir-triphosphate, is a potent inhibitor of viral DNA polymerase
• What is the limation of E. Coli?

  cannot perform post-translational modifications such as glycosylations, possible incorrect folding of eukaryotic proteins expressed in E. coli.
• The kingdom includes yeasts, molds, and mushrooms.
• Most fungi are largely invisible to the naked eye, living for the most part in soil, dead matter, and as symbionts of plants, animals, or other fungi.
• fungi perform an essential role in all ecosystems in decomposing organic matter and are indispensable in nutrient cycling and exchange.
• Alcoholic beverages: fermentation of grains to produce beer and of fruits to produce wine. It is now possible to purchase isolated strains of wild yeasts from different wine-making regions