Microbes in Health and Disease Flashcards
Describe the consequences of microbes in the human body
They are important for many normal developmental and biological functions. In the wrong place, with wrong activity, and in the wrong quantity, they can cause toxicity and pathology. They do this in a number of ways - exhausting critical resources, invasion and killing of cells, production of toxins.
What things do we need to take into consideration when developing antimicrobials?
We need to stop growth or kill microorganisms in order to treat/prevent infections. This needs to be done without being toxic to human cells - the antimicrobial agents need to have selective toxicity for microorganisms and not have adverse effects on health.
What are the different types of microorganisms and how do they differ?
Bacteria, Fungi, Protozoa, Helminths, Mammals. They differ in their size, the location of their genetic info (plasmid, chromosomes in nuclei, chromosomes in micro/macromolecules), ribosomes, mitochondria, cell wall, and method of replication.
What are antimicrobials?
Antimicrobials are agents that target microbes, which include antibacterials, antivirals, antifungals, antiprotozoals, antihelminthics. Antibiotics are antimicrobials that are naturally occuring.
Describe the properties of bacteria
They are unicellular, they don’t have membrane bound organelles or a nucleus. They have ribosomes, but they are of a different composition. Bacteria perform a wide range of biochemical reactions - including some animals cannot. Bacteria and animals can act syngeristically, and bacteria are arguably commensal. Depending on environmental stressors, quantity, or being in the wrong place, some bacteria can be pathogenic.
Describe how bacteria can be classified
Either gram positive or negative depending on their retention of the gram stain. Positive = thick peptidoglycan outside, negative = thin peptidoglycan sandwich. Coccus is sphere, diplo = two, tetrad, strepto = oligo. Bacillus is rods horizontal, palisades are vertical. Comma, vibrio is upside down horseshoe, club rod is sperm shape.
Describe the concept of a magic bullet and the principle ways to target microorganisms
A magic bullet is an ideal agent - one that only targets microorganisms. We can target microbes by stopping genetic material replication, restricting genetic material component availability, compromising cell structural integrity, preventing membrane synthesis needed for growth, preventing cellular protein synthesis
What are the 3 classes of antimicrobial agents?
Class I - Target metabolic precursor production from substrates like glucose, preventing downstream processes.
Class II - Target processes involved in the production of small molecules from metabolic precursors.
Class III - Target processes involved in the production of macromolecules from small molecules.
Describe the structure of a bacterial cell wall
Cell walls are made from peptidoglycan, which is an alternating chain of N-acetylglucosamine and N-acetylmuramic acid bonded by B-(1,4)-glycosidic linkages. These polymers are cross-linked by peptide chains ending in D-alanine, which causes them to form a mesh like structure.
What is the function of B-lactam drugs and what is their mechanism of action?
B-lactam drugs are cell wall synthesis inhibitors and they form covalent bonds with DD-transpeptidase enzymes which inhibits cell wall synthesis.
Describe the common structure of B-lactam drugs and give some examples
The common structure is the B-lactam ring for which the drug family is named. It is a 4 membered ring with a N in the corner. Penicillin is the most common B-lactam drug and having different sidechains attached to penicillin can result in a new drug, such as ampicillin. Vancomycin and Teicoplanin are also examples of cell wall disruptors and they form strong H bonds with the crosslinking peptides.
Give examples of and outline the mechanism of action of cell membrane disruptors
Daptomycin is amphiphatic, it has a hydrophilic peptide ring and a hydrophobic alkyl chain. This allows it to localise in the cell membrane. Aggregation of multiple daptomycin molecules in the cell membrane distorts it and causes a loss of integrity. This causes depolarisation, and chemical gradients are not maintained, so biochemical reactions cannot proceed and the cell dies. Polymixins also work in the same way, and they bind to lipopolysaccharides (abundant in gram neg bacteria). Have many off-target effects so not used as much anymore.
Give examples of and describe the mechanism of bacterial protein synthesis inhibitors.
The differences in bacterial and eukaryotic ribosomes are sufficient enough for drugs to selectively target bacteria, and they can do this by disrupting various processes in the protein synthesis pathway. The classes of drugs are Tetracyclines and Aminoglycosides which target the 30S subunit, they have four connected and functionalised hydrocarbon rings, and amino modified glycosides. Macrolides and other families target the 50S subunit, having macrocyclic lactone ring with 1+ deoxy sugars, being small molecules or small steroids.
Give some examples of Nucleic Acid action and synthesis inhibitors and describe their mechanism of action
Folic acid is critical to DNA & RNA synthesis. Folic acid is synthesised from p-aminobenzoic acid. Enzymes involved are dihydropteroate synthetase and dihydrofolate reductase are the enzymes that convert these molecules to DNA and RNA. Sulfonamides are similar to PABA and Trimethoprim is structurally similar to folic acid, meaning they are competitive inhibitors for the enzymes, hence reducing the rate of DNA/RNA synthesis, slowing down the growth of the bacteria
Explain how DNA gyrase inhibitors work and give some examples
Bacterial replication requires DNA Gyrase (Topoisomerase II). Quinolones like ciprofloxaci, norfloxacin and nalidixic acid inhibit Topoisomerase II preventing replication, making them bacteriostatic (Stopping bacterial growth)
