Why are not all E. coli resistant to antibiotics?

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:

Be nice to editors who ask for your help

I just sent out a decision on behalf of a journal. It was a rejection, which made me a bit sad, but I am happy the task if off my to do list.

I haven’t often played the role of editor, but this manuscript I edited gave me a new appreciation for the work involved in editing. The decision for this paper was fairly easy because the two reviewers completely agreed. What was really hard was finding the reviewers! I ended up inviting 16 reviewers. 14 declined or didn’t answer, only the last two agreed to do the review.

I got a lot of help from the journal and many of the reviewers who declined helped by suggesting someone else who could do the review, but it was still a lot of (not very interesting) work and I am not very eager to do more editing any time soon.

I do plan to be nicer to the editors who ask for my help, though! Here are three things that we can all do that makes life for editors a little easier:

1. If you’re going to decline to do a review, do so as soon as possible. If the invitation to review is just sitting in your inbox, this is really annoying for the authors and for the editor.
2. If you can’t do the review, take a minute to suggest another reviewer to the editor. Chances are you know more people who could do the review than the editor does. Even if the name you jot down seems utterly obvious to you, the editor may not have thought of this person.
3. If you could do the review, but not in the 10 or 14 days allotted to you, the editor is probably more than happy to give you more time, so you should ask.