Antibiotics in the food supply Flashcards
What was the first antibiotic and when it was discovered?
Discovered in 1928, penicillin
Why antiobiotics is not a simple question/answer?
What three sites antibiotics can attack
Cell wall, DNA or ribosomes
Bactericidal antibiotics target what site?
Cell wall
Name drugs for cell wall antibiotics
Name drugs targeting DNA of bacteria
Name drugs that target ribosomes
How much of all antibiotics used are in agriculture in Canada
80%
How beta-lactams resistance work
- In the absence of a beta-lactam antibiotic, transpeptidases, also known as penicillin binding proteins catalyze the cross links between glycan changes in the peptidoglycan
- The result is covalent bonds between the peptide and sugar chains that create a rigid cell wall that protects the bacterial cell from osmotic forces that can result in cell rupture
- Beta-lactam antibiotics, are similar to the natural peptidoglycan subunits (D-Ala-D-ala) that are the substrate for the transpeptidases.
- These antibiotics bind strongly to the active site in the transpeptidase and stop cell wall synthesis
What structure is very important in penicillin and synthetic beta-lactams for binding?
Beta-lactam ring
How synthetic alternatives to penicillins are made?
Chemical modification of the structure of penicillins led to the development of synthetic beta-lactams – which have greater spectrums of activity, and greater resistance to beta-lactamases, as well as different pharmacokenetic properties
How general resistance to beta-lactams can develop?
- Penetration – Intracellular bacteria are resistant to beta-lactams if they are in a mammalian cell
- Porins – Gram-negative bacteria are resistant to beta-lactams since the outer cell membrane protects the peptidoglycan, but porins can allow beta-lactams inside. However, some Gram-negatives have smaller porins that excludes beta-lactams (general)
- Pumps – Gram-negative bacteria can express ABC transporters to pump antibiotics out of the cell
- Peptidoglycan is absent – Some bacteria like mycobacteria lack a cell wall, and are thus not affected by beta-lactam antibiotics
what are two specific resistance to beta-lactams?
- Penicillinases – Some bacteria can make beta-lactamases that degrade beta-lactam antibiotics before they reach the cell
- PBPs – Some bacteria can express mutated transpeptidases that still has the enzymatic activity for cell wall synthesis, but does not bind to beta-lactam antibiotics
Two types of resistance to antibiotics:
General and specific
Type of mechanisms for AMR, Action (specific or non specific) and what antibiotics are prone to it?
DNA gyrase is an essential bacterial enzyme that catalyzes the ATP-dependent negative super-coiling of double-stranded closed-circular DNA.
RNA polymerase is an enzyme that is responsible for copying a DNA sequence into an RNA sequence
Beta lactamase and cephalasporinases act on the antibiotic
The timeline of antibiotics invention and use
- Sulfonamides were first marketed as Antibiotic Growth Promoters (AGPs) in 1938
- Gramicidin was successfully used to treat a mass outbreak of mastitis in dairy cows in 1940
- In 1948, sulfaquinoxaline was the first antibiotic licensed for inclusion in poultry feed to prevent coccidiosis
- A few years later, it was shown that subtherapeutic doses had growth promoting effects in poultry
- In the 1950s the beef industry switched from low-density grazing to high-intensity feed-lot systems
- Chlortetracycline, oxytetracycline, and bacitracin all used at some point
- Bacitracin and ionophores still commonly used
- Between 1951 and 1970 agricultural use of antibiotics increased >30-fold
In what countries Antibiotic growth promoters (AGPs) are banned
Sweden and other nordic countries
What antibiotics are banned in US; China and India?
- USA has banned the use of cephalosporins and fluoroquinolone in agriculture and has also released guidelines to phase out antibiotic use
- India and China have banned colistin use in agriculture, and are attempting to phase out AGPs