Salmonella (specifically S. typhimurium) is a wonderful model organism for a couple reasons. First of all our main goal is actually how to find an antibiotic that kills S. Typhi. These two different serovars are different because, in humans, S.typhimurium causes food poisoning while S.typhi is much more serious and can often be fatal. The two are structurally identical therefore the drug we test against the safer S. Typhimurium will also work in S. Typhi. S. Typhimurium is also a great bacterium to use in antibiotic testing because it causes typhoid like symptoms in mice not humans. This allows us to gather reliable results for testing our drug against S. Typhi in the safest way possible.
By doing a max dose experiment, we tested Mitomycin only at amounts that are safe for humans. We were able to establish what amount is safe using the therapeutic index which compares affective does and max toxicity. The TI tells us the max effective dose without being toxic to humans.
Great Job! How do you think this work potentially relates to find a “cure” for antibiotic resistance? How do you think drugs specifically target infected or damaged cells? Could changes in cell surface proteins be a part of this?
Specifically we are looking for a more efficient (less prone to antibiotic resistance) antibiotics against the disease typhoid fever. There is no “cure” for antibiotic resistance since we cannot completely stop a bacterium from naturally mutating. In using a chemotherapeutic drug, I would assume that the drug is not fully capable of determining which cells are good (healthy cells) or bad (bacterium cells). It really is about weighing harms and benefits. If you are dying from typhoid fever, some damage to regular cells that will eventually be replaced by healthy cells once the drug is discontinued, would be worth using a drug that may harm other healthy cells.
Great job! Where would you start in doing more dose experiments in determining the most effective dose (i.e. what doses would you think it’d be beneficial to focus on?)
The doses we would focus on are the ones that gave statistical hits (data lies +/- 2 standard deviations from the mean absorbance of DMSO at 20 percent). In our specific experiment, I think the most beneficial dose to focus on would be 10 micro molar because it was the hit that killed the most bacteria.
Mitomycin most likely works like other cancer drugs in the way that it stops malicious cells from dividing by disrupting/damaging the RNA and DNA. If the bacteria cell does not have the genetic “instructions” to make more of itself it cannot reproduce and if the bacterium cannot reproduce it will die.
Mitomycin most likely attacks salmonella by damaging the bacteria’s DNA and RNA. This is how many chemotherapeutics work therefore this would be my best guess of the mechanism in which mitomycin uses to attack malicious cells. When the bacterium cannot use its damaged DNA and RNA it cannot reproduce because it now does not have the genetic “instructions” to do so. If the bacterium cannot reproduce it will die.
Hello! I was wondering why you guys specifically used salmonella as your host bacteria? Did it have to do with evolutionary similarity?
Salmonella (specifically S. typhimurium) is a wonderful model organism for a couple reasons. First of all our main goal is actually how to find an antibiotic that kills S. Typhi. These two different serovars are different because, in humans, S.typhimurium causes food poisoning while S.typhi is much more serious and can often be fatal. The two are structurally identical therefore the drug we test against the safer S. Typhimurium will also work in S. Typhi. S. Typhimurium is also a great bacterium to use in antibiotic testing because it causes typhoid like symptoms in mice not humans. This allows us to gather reliable results for testing our drug against S. Typhi in the safest way possible.
Even though mitomycin is effective at killing the salmonella could the mitomycin kill healthy cells it comes into contact with?
By doing a max dose experiment, we tested Mitomycin only at amounts that are safe for humans. We were able to establish what amount is safe using the therapeutic index which compares affective does and max toxicity. The TI tells us the max effective dose without being toxic to humans.
Great Job! How do you think this work potentially relates to find a “cure” for antibiotic resistance? How do you think drugs specifically target infected or damaged cells? Could changes in cell surface proteins be a part of this?
Specifically we are looking for a more efficient (less prone to antibiotic resistance) antibiotics against the disease typhoid fever. There is no “cure” for antibiotic resistance since we cannot completely stop a bacterium from naturally mutating. In using a chemotherapeutic drug, I would assume that the drug is not fully capable of determining which cells are good (healthy cells) or bad (bacterium cells). It really is about weighing harms and benefits. If you are dying from typhoid fever, some damage to regular cells that will eventually be replaced by healthy cells once the drug is discontinued, would be worth using a drug that may harm other healthy cells.
Great job! Where would you start in doing more dose experiments in determining the most effective dose (i.e. what doses would you think it’d be beneficial to focus on?)
The doses we would focus on are the ones that gave statistical hits (data lies +/- 2 standard deviations from the mean absorbance of DMSO at 20 percent). In our specific experiment, I think the most beneficial dose to focus on would be 10 micro molar because it was the hit that killed the most bacteria.
Great presentation. By what mechanism do you think Mitomycin attacks the salmonella bacteria?
Mitomycin most likely works like other cancer drugs in the way that it stops malicious cells from dividing by disrupting/damaging the RNA and DNA. If the bacteria cell does not have the genetic “instructions” to make more of itself it cannot reproduce and if the bacterium cannot reproduce it will die.
Mitomycin most likely attacks salmonella by damaging the bacteria’s DNA and RNA. This is how many chemotherapeutics work therefore this would be my best guess of the mechanism in which mitomycin uses to attack malicious cells. When the bacterium cannot use its damaged DNA and RNA it cannot reproduce because it now does not have the genetic “instructions” to do so. If the bacterium cannot reproduce it will die.