MEDCHEM E CHEM BIO LECTURE 1

• Microorganisms


  Microscopic or sub-microscopic organisms that are 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

  
• 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" and grow quickly
  • 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


  The long, branching filamentous structure of a fungus that makes up the mycelium
• Fungi in research


  • Important model organisms
  • Used to prove the "one gene, one enzyme" hypothesis
  • Useful in studying circadian rhythms, epigenetics and gene silencing
• 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 serious for humans, leading to the development of the field of infectious diseases
• Antibiotics


  Chemotherapeutic or antimicrobial agents with activity against microorganisms, but not viruses
• Alexander Fleming discovered penicillin, the first antibiotic, in 1928
• Bacteriostatic and bactericidal antibiotics

  Bacteriostatic antibiotics stop bacteria from multiplying, while bactericidal antibiotics kill bacteria
• Antibiotics work by exploiting the differences between microbial and human cells
• 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
• 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. Crystal violet stains all cells blue/purple

  4. Organic solvents extract the blue dye complex from the lipid-rich, thin walled gram negative bacteria

  5. Application of counter stain (safranin) stains the decolorized gram-negative cells red/pink, the gram-positive bacteria remain blue
• Penicillins


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


  • One of the amino acid residues (a serine, -OH in the side chain) in the active site of a bacterial enzyme reacts with penicillin forming an irreversible covalent bond
  • The enzyme is now completely inactivated and unable to perform its reaction
  • The cell wall of the bacteria cannot be expanded and the cell eventually explodes
• 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 can be acquired

  • Via natural selection acting upon random mutation
  • Via a donor cell's plasmid (circular unit of DNA), which has a resistance gene
• Aminoglycoside-modifying enzymes catalyze the covalent modification of specific amino or hydroxyl functions, leading to a chemically modified drug which binds poorly to ribosomes
• Semi-synthetic antibiotics


  Sometimes it is sufficient to synthesise a slightly different molecule to re-establish activity, the modified drug is sufficiently different from the original one that it is not recognised anymore by the target molecule (i.e. an enzyme)
• Antibiotics cannot kill viruses because bacteria and viruses have different mechanisms and machinery to survive and replicate
• Antiviral drugs


  A class of medication used specifically for treating viral infections, they are relatively harmless to the host
• How antiviral drugs work

  Target stages in the viral life cycle (i.e. viral attachment to host cell, uncoating, synthesis of viral mRNA, translation of mRNA, replication of viral RNA and DNA, maturation of new viral proteins, etc.)
• Acyclovir


  • A guanine analogue antiviral drug used for the treatment of herpes simplex virus infections
  • It is a synthetic deoxyguanosine analog and it is the prototype antiviral agent that is activated by viral thymidine kinase
  • The final product, acyclovir-triphosphate, is a potent inhibitor of viral DNA polymerase
• Acyclovir triphosphate competitively inhibits viral DNA polymerase and competes with the natural deoxyguanosine triphosphate, for incorporation into viral DNA