Hello! Thank you for this question! Short term directions to establish repeatable statistical hits and to further replicate the cell environment within a macrophage, as well as our long term directions to understand TKI’s more, all have the end goal of eventually allowing our compounds to be approved antibiotics! This is optimistic, but this work is part of the fight against bacterial resistance by introducing new tools.
Absolutely! I would like to retest this experiment more to affirm our data, thereby establishing repeatable statistical hits, as well as do a similar test but introducing the peptide polymyxin to the media to replicate the cell environment within a macrophage. Hopefully the peptide will “help” the compounds kill the Salmonella Typhimurium! Thank you for this question!
Hi! These potential antibiotics are different from others in the way it works to limit signaling growth in cells. All of our compounds generally work by inhibiting tyrosine kinase enzymes, but each differ in how they go about it, and what they “specialize” in, so to speak. For example, in the case of Dasatinib, one of the compounds which proved to be a negative hit, is an ATP-competitive protein tyrosine kinase inhibitor which treats chronic myeloid leukemia.
What can be learned more about these compounds is how their chemo therapy properties can carry over to antibiotic properties as well. A long term goal of ours is to identify the specific biochemical pathways affected in Salmonella Typhimurium when exposed to TKIs. The viability of TKIs as antibiotics are highly dependent on the selective mode of inhibition, therefore understanding how this mechanism interacts with bacteria is crucial to determining which will be the most effective.
Thank you for these questions!
How could your future directions be applied to real world pharmaceuticals? Where the results from your lab what you expected based on the lab you referenced?
Hello! Our future directions will hopefully lead to our compounds being approved antibiotics, should further testing provide further evidence towards our compounds antibiotic properties.
The labs we referenced detailed our compounds chemotherapeutic properties, not necessarily their antibiotic ones, so we went into this with an open mind. The hypothesis was that their chemotherapeutic properties, specifically the fact that they limit signaling growth in cells, would also work as antibiotic properties. Dasatinib and sorafenib seemed to affirm this initial hypothesis, but further testing should be done to reach more conclusive results, as outlined in the future directions. Thank you for these questions!
Great job! You guys clearly know what you’re talking about.
Thank you very much!
What do your future directions mean in terms of the big picture of this research?
Hello! Thank you for this question! Short term directions to establish repeatable statistical hits and to further replicate the cell environment within a macrophage, as well as our long term directions to understand TKI’s more, all have the end goal of eventually allowing our compounds to be approved antibiotics! This is optimistic, but this work is part of the fight against bacterial resistance by introducing new tools.
Are there any other experiments you would like to run to further test the effectiveness of this antibiotic?
Absolutely! I would like to retest this experiment more to affirm our data, thereby establishing repeatable statistical hits, as well as do a similar test but introducing the peptide polymyxin to the media to replicate the cell environment within a macrophage. Hopefully the peptide will “help” the compounds kill the Salmonella Typhimurium! Thank you for this question!
What more could be learned about this antibiotic? How is this antibiotic different than others?
Hi! These potential antibiotics are different from others in the way it works to limit signaling growth in cells. All of our compounds generally work by inhibiting tyrosine kinase enzymes, but each differ in how they go about it, and what they “specialize” in, so to speak. For example, in the case of Dasatinib, one of the compounds which proved to be a negative hit, is an ATP-competitive protein tyrosine kinase inhibitor which treats chronic myeloid leukemia.
What can be learned more about these compounds is how their chemo therapy properties can carry over to antibiotic properties as well. A long term goal of ours is to identify the specific biochemical pathways affected in Salmonella Typhimurium when exposed to TKIs. The viability of TKIs as antibiotics are highly dependent on the selective mode of inhibition, therefore understanding how this mechanism interacts with bacteria is crucial to determining which will be the most effective.
Thank you for these questions!
How could your future directions be applied to real world pharmaceuticals? Where the results from your lab what you expected based on the lab you referenced?
Hello! Our future directions will hopefully lead to our compounds being approved antibiotics, should further testing provide further evidence towards our compounds antibiotic properties.
The labs we referenced detailed our compounds chemotherapeutic properties, not necessarily their antibiotic ones, so we went into this with an open mind. The hypothesis was that their chemotherapeutic properties, specifically the fact that they limit signaling growth in cells, would also work as antibiotic properties. Dasatinib and sorafenib seemed to affirm this initial hypothesis, but further testing should be done to reach more conclusive results, as outlined in the future directions. Thank you for these questions!