What are the challenges faced while predicting antibiotic resistance on bacterial genome sequences?

Question

[mrinsmrids]

While developing antibiotic resistances,what are going to be the challenges faced by the Biologist while performing it over bacterial genome sequences?

[Mensur Dlakic]

I think this is a homework question that is purposely posed in general way, in which case no soup for you. If not, it would help to narrow it down and ask a question more clearly and specifically. I assume you mean for biologists while looking for antibiotic resistance in genomes, but there are other interpretations.

[mrinsmrids]

Hahaha, yes. It was part of my interview question which I couldn't quite get a hang of and I was searching which platform would be the best to ask such questions. The interview is over and but this question was still stuck in my head. Yes , so while Biologists are making antibiotics to make them resistant to certain diseases, how do they predict the resistant properties on things like bacterial genome sequences?

Answer 1

[Mensur Dlakic]

When you asked this the first time, I thought it was simply a shorthand question because you didn't want to go into details. Now it seems more likely that you are mixed up about some of these concepts, as you are asking about something that doesn't really happen in real life.

First, biologists are rarely making antibiotics - most of them are natural products that may be slightly modified, and mostly by chemists. Bacteria and fungi make antibiotics as a way of competing with each other, so they actually kill microorganisms rather than making them resistant to certain diseases. Again, we co-opted this killing property of natural products for our own benefit.

As to predicting resistance from bacterial sequence, for most antibiotics we know how they kill bacteria, and for many of them we know how bacteria develop resistance. Without getting into the weeds, in most cases they are proteins that either: 1) modify or break down the antibiotics; 2) modify its target molecule so it has no substrate to work on; 3) pump the antibiotic out of the cell. Those proteins are of known sequence and often of known structure, so one can look for them in bacterial genomes (and plasmids) and predict whether these organisms are likely to be resistant.

[mrinsmrids]

@Mensur Dlakic Thank you so much for the clear-cut explanation! So, you mean to say that these bacterial genome sequences get adapted over time to resist the antibiotic right? In that case, to prevent this from happening, how are the chemists going to synthesize a drug that could detect the bacteria's aforementioned 3 activities and provide resistance to these. Or if I mistook it wrong, do you mean to say that these proteins that are present are part of the antibiotic that does the above 3 activities that prohibits the bacterial genomes to become resistant to the antibiotic? If so, what are these proteins called?