Microbiology: Bacteria Flashcards
………. spectrum antibiotics target across the Gram types
…………. spectrum target only one Gram type.
Broad
Narrow
Define Bactericidal
Kills the organism
Example penicillin’s, cephalosporin’s
Define Bacteriostatic
Drugs that temporarily inhibit the growth of an organism (i.e. reversible if removed).
Examples Tetracycline’s, Chloramphenicol
Some antibiotics require the bacteria to be growing to kill them. For example…..
β-lactams e.g. Ampicillin (bactericidal antibiotic)
If you use Beta-lactams in combination with a bacteriostatic antibiotic then the Beta-lactam will not kill the bacteria. When therapy is removed the bacteria will start growing again.
Define minimum inhibitory concentration (MIC)
the concentration required at the site of infection to achieve bacterial inhibition
Define minimum bactericidal concentration
is the concentration required at the site of infection to kill the bacteria
E. coli in an abscess growing anaerobically is more resistant to gentamicin than aerobically grown E. coli Why?
They do not express a specific oxidative transport system anaerobically which aids antibiotic entry to the bacterial cell.
Bacteria growing in biofilms may be protected because….
The antimicrobials can not penetrate deep into the film
Highly lipid soluble drugs can…..
penetrate cells. These will have large volume distribution (e.g. tetracycline’s; macrolides, Quinolones)
Water soluble antibiotics remain…..
…..confined to blood and extracellular fluids. (e.g. aminoglycosides, Beta-lactams)
What are Maximum Residue Levels (MRL)?
There are restrictions on use of antimicrobial in food producing animals
Residues can get through to food.
Therefore there are with holding times before treated animal can enter a food chain
What are some side effects of antibiotics?
Nephrotoxicity (Aminoglycosides) Tendon damage (Quinolones) Liver disturbances (Rifampicins)
What are the secondary effects of Rifampicin?
Rifampicin is metabolized in the liver where it’s a potent inducer of the P450 pathway.
Rifampicin is an effective liver enzyme-inducer, promoting the up regulation of hepatic cytochrome P450 enzymes.
This increases the rate of metabolism of many other drugs normally cleared by the liver
Rifampicin is red and can cause redness in body fluids.
Where do antibiotics act?
Image in notes
What are the wall targeting antibiotics?
Beta lactams
Peptide antibiotics: Glycopeptides, Vancomycin
Bacitracin
Teixobactin
What do beta lactams target?
Penicillin binding protein (A transpeptidase) which stops peptide cross links in the wall
What do peptide antibiotics target?
Directly interacts with cell wall D-Ala preventing synthesis of NAG/NAM polymers
What is special about Vancomycin?
It is on WHO’s protected list
What is the ole of peptidoglycan?
Peptidoglycan serves a structural role and counteracts the osmotic pressure of the cytoplasm.
How does beta lactam work?
In Gram positive direct access to wall.
In Gram –ve requires porin to access wall though outer membrane.
1. Binding cell receptors PBP (penicillin binding proteins)
2. Inhibits transpeptidation in cell walls peptidoglycan.
3. Peptide precursors accumulate.
4. This accumulation can triggers autolysin activity
5. Positive pressure on weakened wall leads to cell lysis.
Penicillins are organic acids they are available as the soluble salts of the acid. They are ionized in serum therefore they…
Spread well in extracellular fluids and are poor at crossing membranes
Eliminated almost entirely by the kidneys so high level in urine (except nafcillin excreted in bile)
Penicillins are organic acids they are available as the soluble salts of the acid. They are ionized in serum therefore they…
Spread well in extracellular fluids and are poor at crossing membranes
Eliminated almost entirely by the kidneys so high level in urine (except nafcillin excreted in bile)
What is different about cephalosporin to penicillin?
Resistant to β-lactamase produced by Staphylococcus.
But extended spectrum β-lactamases (ESBLs) can target.
Can be used on patients hypersensitive to penicillin.
How does Bacitracin work?
Bacitracin interferes with the dephosphorylation of an isoprenyl pyrophosphate carrier (bactoprenol)
Bactophenol is membrane carrier molecule that transports the building-blocks of the peptidoglycan bacterial cell wall across the inner membrane
What formulations does bactracin come in?
Causes nephrotoxicty – limited to topical and ophthalmic preparations
Is bactracin susceptible to resistance?
Resistance develops slowly and is rare.
What are the cell membrane targeting antibiotics?
- Polymyxins
2. Antimicrobial peptides
How do polymixins work?
They disrupt bacterial cell membrane by interacting with its phospholipids
Target Gram-negative bacteria as they interact with LPS in the outer membrane
What are the narrow spectrum penicillins?
Penicillin- G (benzylpenicillin G)
Penicillin-V (phenoxmethyl-penicillin)
What are the penicillinase (Beta lactamase produced by S. aureus) stable penicillins?
Methicillin
Cloxacillin
What are the broad spectrum penicillins?
Ampicillin
Carbenicillin
What generation of cephalosporins are protected?
3rd and 4th
How do antimicrobial peptides work?
Gram-negative bacteria the peptide first interacts with the lipopolysaccharide molecules of the outer membrane. The outer membrane is permeabilized allowing the peptide to be captured inside.
Gram-positive bacteria. The peptide appears to be attracted by teichoic and by other anionic groups found externally on the peptidoglycan layer.
What type of ribosomes do prokaryotes have?
Prokaryotes have 70S ribosomes, each consisting of a small (30S) and a large (50S) subunit.
What type of ribosomes do eukaryotes have?
Eukaryotes have 80S ribosomes, each consisting of a small (40S) and large (60S) subunit
How do ribosome (protein synthesis) targeting antimicrobials work?
Selective activity due to structural differences between the 80S (eukaryotic) and 70S (prokaryotic) ribosome.
Most antibiotics you use bind to either the 30S or 50S subunits or in some cases to ribosomal complex proteins required for correct function.
What are the bactericidal ribosome targeting antimicrobials?
Aminoglycosides: Steptomycin, neomycin
Nitrofurans
How do aminoglycosides work?
Bind the 30s and effect a number of steps in protein synthesis leading to non-functional proteins
Causes reversible inhibition
What are the bacteriostatic ribosome targeting antimicrobials?
Tetracyclines: Oxytetracycline, Doxycycline
Chloramphenicol
Macrolides: Erythromycin, Tylosin
Lincosamides and pleuromutilins
How does resistance to ribosome targeting antibiotics occur?
Alteration of Target:
Resistance can be intrinsic due to lack of correct receptor domain (sequence) in ribosome.
In some cases intrinsic due to methylation of binding site.
Alteration of Drug
Extrinsic resistance may be due to acquisition of degradative enzymes.
Drug modifying enzymes
How does Rifampicin work?
It acts on the DNA dependant RNA polymerase which blocks the initiation protein synthesis
How do sulphonamides/ trimethoprim work?
competitively inhibit dihydrofolate synthesis chichis required for DNA synthesis
How do Quinolone and novobiocin work?
Bind and stop DNA gyrase which blocks DNA synthesis
How does nitroimidazoles work?
Causes DNA strand breakage
Does NOT work on aerobic bacteria as will not be reduced.
What do ahminoglycosides require to be taken up by the bacteria?
aerobic respiration
