Antibiotics in the food supply

Question 1

what are beta-lactams and what is their function?

Answer 1

beta-lactams are an antibiotic that bind to transcriptase’s active site in the bacteria’s peptidoglycan layer. by binding to the active site, they inhibit enzyme activity associated with cross-linking and cell wall synthesis

Question 2

what are transpeptidases?

Answer 2

penicillin binding proteins that 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

Question 3

what does the molecular structure of beta-lactams signify?

Answer 3

natural peptidoglycan subunits (D-Ala-D-aca) that are the substrates for the transpeptidases. these antibiotics bind strongly to the active site in the transpeptidase and stop cell wall synthesis

Question 4

what is the molecular make-up of beta lactams?

Answer 4

core 4-member beta-lactam ring
the ring is what mimics the shape of the terminal D-Ala-D-ala peptide sequence that is the substrate for the transpeptidase

Question 5

What are the resistance mechanisms to beta-lactams?

Answer 5

1. penetration - intracellular bacteria are resistant to beta-lactams if they are in a mammalian cell
2. porins - gram-negative bacteria are resistant to beta-lactams since the outer cell membrane protects the peptidoglycan
3. pumps - gram negative bacteria can express ABC transporters to pump antibiotics out of the cell
4. peptidoglycan is absent - some bacteria like mycobacteria lack a cell wall, and are thus not affected by beta-lactam antibiotics

Question 6

what do bacteria produce as specific resistance mechanisms to beta-lactams?

Answer 6

1. penicillinases - some bacteria can make beta-lactamases that degrade beta-lactam antibiotics before they reach the cell
2. 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

Question 7

what are the general mechanisms of AMR?

Answer 7

Export, destruction, modification, altered receptors, and membrane composition

Question 8

what is the general timeline/ history of different antibiotics being produced?

Answer 8

1930s- sulfonamides
1940s- beta-lactams, aminoglycosides
1950s- chloroamphenicol, tetracycline, glycopeptides, macrolides
1960s- streptogranins, quinolones, lincosamides
1970s- trimethoprim
2000s- cyclicipopeptides, oxazolidinones
2015- teixobactin

Question 9

what is the history of antibiotics in agriculture?

Answer 9

Sulfonamides were first marketed as antibiotic growth promoters in 1938. Gramicidin was used to treat a mass outbreak of mastisis in 1948, and 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
between 1951 and 1970, agricultural use of antibiotics increase more than 30 fold

Question 10

what is most cattle treated with in the US and Canada?

Answer 10

intramammary ceftiofur hydrochloride and penicillin combinations after each lactation to prevent mastisis- known as blankey dry cow therapy

Question 11

what does each categorial class signify in antibiotics?

Answer 11

Category 1- very high importance

category IV- low importance

Question 12

in what decades did AMR start increasing?

Answer 12

The 1960s-2000s

Question 13

does banning antibiotics work?

Answer 13

Yes, there is leveling off and even a decrease of the AMR in the community. but banning based on category may be problematic, the use of category IV antibiotics can also contribute to medically important antibiotics in both human and veterinary use

Question 14

what is the significance to ceftiofur?

Answer 14

an antibiotic that was used in the poultry industry, but banned due to a growing detection of salmonella and e. coli resistant to 3rd generation cephalosporins. the ban ended up resulting in a decrease of AMR

Question 15

what are cephalosporins?

Answer 15

a group of semi-synthetic broad-spectrum antibiotics resembling penicillin

Question 16

what is the significance of Virginiamycin and Bacitracin?

Answer 16

commonly used in poultry and swine industries

Question 17

is it worth it to ban antibiotics?

Answer 17

antibiotics make food cheaper and don’t call for as much land requirement for agriculture industries. AGPs also improve growth rate in pigs by about 4.2% and prevent mastisis. however, this can also be done by better biosecurity since antibiotic is used to compensate for poor hygiene

Question 18

how are ARGs (antibiotic-resistant genes)

Answer 18

through water, soil, farmers, and food
manure, containing manure resistomes are than applied onto soil. The soil and manure are fed antibiotics where raw vegetables grow. crop resistomes develop and now these vegetables now also contain ARGs.

Question 19

what specifically happens when manure is spread onto soil?

Answer 19

ARGs and ARBs mix with environmental ARGs and ARBs, and if they are selected for can become antimicrobial-resistant. current manure resistant techniques are ineffective at removing ARGS from the manure

Question 20

what bacteria are prevalent in organic farming (no antimicrobials)?

Answer 20

Salmonella, Toxoplasma, and Campylobacter

Question 21

what are the two schools of thought on AMR in the food chain?

Answer 21

the food chain either propagates or does not propagate AMR infections in humans.
Questioning whether or not AMR pathogens in food actually contributes to AMR in humans. Number of AMR pathogens in food is very small but the AMR gene pool in food is very high so humans are continuously being exposed to AMR genes through the food chain.

Question 22

what is Colistin?

Answer 22

also known as polymyxin E, an old antibiotic that was not used in humans due to kidney toxicity but due to the spread of AMR became more prevalent in the 1990s. it remains a last resort antibiotic for multi-drug resistant Pseudomonas aeruginosa, klebsiella pneumoniae, and acinetobacter in emergency situations, despite its toxicity.

Question 23

what gene represents the colistin resistance gene?

Answer 23

mcr-1 - confers plasmid-mediated resistance to colistin. this is bad because mcr is capable of HGT and is now present in several species of bacteria

Question 24

what are the methods of detecting AMR?

Answer 24

1. Disk diffusion method
2. MIC test strips
3. sensititre MIC plate

Question 25

what is the disk diffusion method?

Answer 25

use of antibiotic disks which are placed on agar plates containing a lawn of bacteria, and the plate is left to incubate to determine any potential zones of inhibition. the zone diameter is analyzed and compared to a database of zone standards to determine how susceptible the bacterium is

Question 26

what do MIC test strips do?

Answer 26

determines the minimal inhibitory concentration (MIC) which is defined as the lowest concentration of a drug at which no visible growth occurs. strips are placed on a bacterial lawn, incubated, resulting in an ellipse-shaped zone of inhibition. where the ellipse meets the strip, signifies the minimal inhibitory concentration

Question 27

what are Sensititre MIC plates?

Answer 27

96-well plates that contain lyophilized antibiotics configured to determine the MIC to a variety of antibiotics. dilutions of bacteria are added and then inspected visually or with a plate-reader to determine MIC for each antibiotic