Frequent use of antibiotics is thought to create selection pressure by clearing susceptible bacteria and allowing resistant bacteria to spread. Simply put, resistant bacteria are being selected for because they are able to survive in the presence of antibiotics (due to a particular advantageous mutation), while nonresistant strains do not. This limits competition for nutrients, etc.. I think a good example is the use of antibiotics to make cattle grow larger. The likelihood of a resistant strain acquiring a spontaneous mutation and multiplying at large rates increases substantially with the use of antibiotics in this setting.
We pipetted 10uM into the wells at first to see if our compound was effective at the maximum achievable dose in human blood serum. Testing above this range would be pointless. We then tested at varying concentrations below this max dose. Our compound showed no growth inhibition, but we still performed dilutions to test for effectiveness at lower concentrations. For the resistance part, we can’t simulate that, nor was it an aim of this experiment.
Hey Mia. We first tested our compound at a dose of 10uM. This is the maximum achievable concentration in human serum for most drugs, so it would be pointless to test concentrations above this value. Although we did not see growth inhibition of S. Typhimurium at this max dose, we performed serial dilutions to test the properties of mefenamic acid at lower concentrations. Creating better resistance was not an aim of this research project.
NSAIDs have shown antibacterial properties in many different studies. Mefenamic acid specifically has shown some promising results in inhibiting the growth of bacteria in vivo, due to the promotion of T-cell mediated immunity. Maybe mefenamic acid depends on living cells and this decrease in prostaglandin levels in the body to have an effect on growth. Although mefenamic acid contains one carboxylic acid group, which is often utilized in pharmaceuticals, the functional groups in the compound did not result in any growth inhibition of S. Typhimurium.
Hi Daniel! That is a great question. Antibiotics usually can be used in more than one way. For example, ampicillin (the positive control) can be administered by three different routes: orally, intramuscularly, or intravenously. Working as a nurse, I would often give intravenous antibiotics for septic infections–the route of administration depends on the severity of the infection. Ideally, I think a good antibiotic should be easy to take at home. In cases of severe infection, IV would be preferred to achieve higher concentrations at the site and quicker absorption of the antibiotic.
What selective pressures increase the antibiotic resistance you’re talking about at the 40 second mark?
Frequent use of antibiotics is thought to create selection pressure by clearing susceptible bacteria and allowing resistant bacteria to spread. Simply put, resistant bacteria are being selected for because they are able to survive in the presence of antibiotics (due to a particular advantageous mutation), while nonresistant strains do not. This limits competition for nutrients, etc.. I think a good example is the use of antibiotics to make cattle grow larger. The likelihood of a resistant strain acquiring a spontaneous mutation and multiplying at large rates increases substantially with the use of antibiotics in this setting.
https://pubmed.ncbi.nlm.nih.gov/11137404/
How do you determine to increase or decrease each substance poured to create a better resistance?
We pipetted 10uM into the wells at first to see if our compound was effective at the maximum achievable dose in human blood serum. Testing above this range would be pointless. We then tested at varying concentrations below this max dose. Our compound showed no growth inhibition, but we still performed dilutions to test for effectiveness at lower concentrations. For the resistance part, we can’t simulate that, nor was it an aim of this experiment.
Hey Mia. We first tested our compound at a dose of 10uM. This is the maximum achievable concentration in human serum for most drugs, so it would be pointless to test concentrations above this value. Although we did not see growth inhibition of S. Typhimurium at this max dose, we performed serial dilutions to test the properties of mefenamic acid at lower concentrations. Creating better resistance was not an aim of this research project.
Why do you think Mefenamic acid was ineffective against the bacteria?
NSAIDs have shown antibacterial properties in many different studies. Mefenamic acid specifically has shown some promising results in inhibiting the growth of bacteria in vivo, due to the promotion of T-cell mediated immunity. Maybe mefenamic acid depends on living cells and this decrease in prostaglandin levels in the body to have an effect on growth. Although mefenamic acid contains one carboxylic acid group, which is often utilized in pharmaceuticals, the functional groups in the compound did not result in any growth inhibition of S. Typhimurium.
How would a drug like this, if effective, be administered in vivo? Would intravenous or oral administration be the preferred route?
Hi Daniel! That is a great question. Antibiotics usually can be used in more than one way. For example, ampicillin (the positive control) can be administered by three different routes: orally, intramuscularly, or intravenously. Working as a nurse, I would often give intravenous antibiotics for septic infections–the route of administration depends on the severity of the infection. Ideally, I think a good antibiotic should be easy to take at home. In cases of severe infection, IV would be preferred to achieve higher concentrations at the site and quicker absorption of the antibiotic.