Last summer gave a talk at a Gordon Conference about transmission and evolution of drug resistance in HIV and E. coli. When I was done with my talk, there was time for questions. Dmitri Petrov asked what I thought about why resistant and susceptible strains of bacteria co-exist. I had to admit that I hadn’t really thought about that.
This question of co-existence (why aren’t all bacteria resistant or all of them susceptible?) it not a new one. In fact, about a week after the Gordon Conference, I talked to Marc Lipsitch who has worked on this question for many years. It was just not on my radar. Until last summer.
The question of co-existence marinated in my head for over the summer. I read papers about it. Looked at the data I was analyzing. And then sometime in the fall it suddenly hit me! I saw a solution to the question that was real easy. This is what I think may be happening: Resistance evolves when a bacterial strain finds itself in a person who is treated with antibiotics. But because most of us aren’t on antibiotic treatment most of the time, these resistant strains tend to have lower R0 values than susceptible strains (that is, the resistant strains don’t spread as effectively). Therefore in the human population at large, existing resistant strains are losing against the susceptible strains.
I had been studying the many origins of resistance (resistance in E. coli and other bacteria evolves very often – lots of convergent evolution), and I had been studying the cost of resistance (I think most resistant E. coli strains tend to die out – thought this is not easy to prove). These two ingredients together can explain the co-existence of resistant and susceptible strains.
Early October I emailed Dmitri: “Dmitri, I think I have the answer to your question!”. Dmitri answered: “Exciting! But you forgot to attach the manuscript”. Me: “Oh, I didn’t write it up yet! It is just in my head.”
So I started writing because that’s how academic science works!
The manuscript now lives on Medrxiv. I have submitted it to Nature (desk-rejected) and to Science (reviewed and rejected). Traditionally, after a rejection from a high-profile journal, one would send a manuscript to another journal right away, but one of the reviewers from Science suggested using a particular Norwegian dataset, instead of the Enterobase data I had used for the manuscript. I really liked that idea (as well as some other ideas from the reviewers). So I decided to pause and do more analysis. Some of the new data made their way into my talk for the TAGC conference in Washington DC last week.
If you are curious to hear where I am at with this project, here is the video of my talk:
Being A Better Scientist 
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