Good question! Unfortunately there is nothing stopping bacteria from developing resistance to this compound if it does prove to be useful antibiotic. Mutations are random and the more a single antibiotic is used, the more likely it is that an antibiotic-resistant bacteria will develop and potentially spread. One way around this is by using more and more different kinds of antibiotics so that the likelihood and risk of antibiotic-resistant bacteria goes down as well as using less antibiotics for things such as livestock. Another way to combat this is by combining different antibiotics so that a bacteria that is resistant to one may still get killed off by the other. However that can also carry its own risk due to being potentially toxic to the patient. The purpose of discovering new antibiotics is to stay ahead of the curve because bacteria are constantly evolving and never stopping so we must continuously develop new antibiotics to keep apace.
At what specific dosage do you think the antibiotic would have to be changed to to be safe enough to use in humans? How would you go about trialing that?
Also a great question! Right now there still needs to be more research done to determine a specific dosage or method of treatment for azacitidine for use as an antibiotic. We did show at what concentrations azacitidine appears to kill off the salmonella typhimurium and where the drop off in effectiveness is, but that could all change in vivo due to unforeseen complications. First, you would have to use mouse models to see if the effective dose is safe for the mice while still fighting the salmonella typhimurium infection. Azacitidine is already used as a chemotherapy drug so hopefully it can be used at lower dosages to kill salmonella in the human body than what is currently used for treating cancer. That would mitigate side-effects and improve the safety for the patients. If it is the same dosage, maybe it could be used as a last resort for antibiotic resistant strains in a worst case scenario. If it is higher though than it would likely not be very useful as an antibiotic at all.
Is there anything stopping bacteria from developing resistance to this antibiotic like other currently used antibiotics? If so is that an issue?
Good question! Unfortunately there is nothing stopping bacteria from developing resistance to this compound if it does prove to be useful antibiotic. Mutations are random and the more a single antibiotic is used, the more likely it is that an antibiotic-resistant bacteria will develop and potentially spread. One way around this is by using more and more different kinds of antibiotics so that the likelihood and risk of antibiotic-resistant bacteria goes down as well as using less antibiotics for things such as livestock. Another way to combat this is by combining different antibiotics so that a bacteria that is resistant to one may still get killed off by the other. However that can also carry its own risk due to being potentially toxic to the patient. The purpose of discovering new antibiotics is to stay ahead of the curve because bacteria are constantly evolving and never stopping so we must continuously develop new antibiotics to keep apace.
At what specific dosage do you think the antibiotic would have to be changed to to be safe enough to use in humans? How would you go about trialing that?
Also a great question! Right now there still needs to be more research done to determine a specific dosage or method of treatment for azacitidine for use as an antibiotic. We did show at what concentrations azacitidine appears to kill off the salmonella typhimurium and where the drop off in effectiveness is, but that could all change in vivo due to unforeseen complications. First, you would have to use mouse models to see if the effective dose is safe for the mice while still fighting the salmonella typhimurium infection. Azacitidine is already used as a chemotherapy drug so hopefully it can be used at lower dosages to kill salmonella in the human body than what is currently used for treating cancer. That would mitigate side-effects and improve the safety for the patients. If it is the same dosage, maybe it could be used as a last resort for antibiotic resistant strains in a worst case scenario. If it is higher though than it would likely not be very useful as an antibiotic at all.