Thank you, Alice. Hope we can catch up soon!

New preprint!

Ever wondered why only a fraction of genomes encode CRISPR immunity? 🧬 🦠

Turns out CRISPR is rarely beneficial against virulent phages, being most beneficial against those for which resistance mutations are rare!

An epic effort by Rosanna Wright

www.biorxiv.org/content/10.1...

Thanks, my friend!

Almost forgot; if you want to hear more about our findings, listen ZaminIqbal speaking at @bbcsciencenews.bsky.social Science In Action here:
www.bbc.co.uk/sounds/play/...

Last but not least. Thanks to all the brilliant coauthors and the four reviewers of this paper. We rarely talk about the latter, but we're thankful for their time, thorough assessment of our work, respectful interactions and insightful feedback that made the study much better.

There's so much to learn about how these fascinating DNA “organisms" (credit to Prof Naomi Datta) we call #plasmids evolve, drive bacterial adaptation and #AMR spread. My current and future work builds on the hundreds of stories still hidden in these historical plasmids. Stay tuned!

Our study is time-travelling enabled by #genomics and the visionary genius of scientists who collected the Murray collection (special mention to Prof Everitt Murray and Prof Naomi Datta - photos below), as well as the efforts of brilliant people who have safeguarded this resource @NCTC

It's been 97 yrs since A. Fleming discovered penicillin, leading the world to the antibiotic era, saving millions of lives. Our work shows the other side of the story: how the widespread use of #antibiotics led to the emergence of global spreaders of #AMR
doi.org/10.1126/scie...

Based on this model, plasmids' remarkable ability of both conservative and high-risk #evolution provides bacteria 🦠 with powerful tools 🛠️ for rapid adaptation: gaining genes 🧬 into stable backbones and constantly trying new forms 🔄. Both strategies have been key to the emergence of #AMR plasmids.

To wrap up, we have synthesised our findings on 100 years ⌛️ of #plasmid evolution into a new model:
Whilst many families remain mostly stable, changing mainly via gene gain/loss and mutation, others break and fuse in a continual (birth/death) process ♻️🧬generating new diversity.

So, have these☝️plasmids and their families contributed the same?
Not quite. Some CFs contain more AMR genes and resistance plasmids. Self-transmissible recombinogenic plasmids have been favoured. And fusion plasmids are the largest collectors of #AMR genes. We can think of these as #Superplasmids

Our data support that resistance #plasmids emerged from selected lineages in a very short evolutionary time during the #antibiotic era and have remained relevant to the antibiotics introduced.
Here are a couple of shocking examples we found (up to 40 #AMR genes in a single plasmid)

But what about #AMR? Wasn't this study about the history of AMR spread?
Whilst virtually all pre-antibiotic era plasmids were devoid of AMR genes, a minority of their modern descendants are flooded with them: we detected >21,000, conferring resistance to both first-line and last-resort #antibiotics

Fusions 🧬🔄 are particularly fascinating because they tend to be massive in size, but most are single instances, suggesting they are only brief snapshots 📸 in time.
Plus, if you try to track what has fused with what... well, it's utter chaos!
So the process is highly dynamic.

So, how have #plasmids changed in the past century?
We identified 3 CF types that define plasmids' fate during the #antibiotic era:
- Disappeared as a whole, but their parts were recycled.
- Stayed roughly the same size.
- Fused and devoured each other, creating complex new diversity.

The historical plasmids ⌛️🧬 and their descendants are highly diverse. We detected 940 close families (CFs) in a similarity network, and their bacterial hosts include several #WHO priority pathogens 🦠🧫. Some CFs contain many plasmids, whilst many others contain only one.

So here are our 🔑 key findings:
* High-risk resistance plasmids ( #Superplasmids ) originated from a minority of ancestors during the antibiotic era.
* In that time, plasmids disappeared, stayed almost the same, or fused.
* Plasmids fuse a lot, and that's key to #AMR spread.
Want to learn more?👇

By contrasting past and present, we show how plasmids adapted to the #antibiotic era and their evolutionary journey.
This is key because plasmids now carry complex arrays of many #AMR genes, but we don't know how we got here or what plasmids looked like in the pre-antibiotic era.

We then looked for modern relatives of our historical plasmids.
We found that ~10,000 contemporary plasmids can be traced back to ancestors already carried by pathogens🦠 in the pre-antibiotic era.
These modern descendants can be found worldwide across numerous bacterial species.

We went back in time ⏪⌛️, as far as 1917, through the unique Murray collection of clinical bacteria from the pre-antibiotic era.
We started by reviving these historical bacteria 🧫🦠, which had been frozen ❄️ since the 80s, to reconstruct the genomes of their plasmids 🧬.

The focus of our study is #plasmids, the primary spreaders of #AMR genes and key elements of bacterial adaptation.
You can think of these as DNA rings that give bacteria #superpowers, including the ability to cause disease and survive multiple #antibiotics.

Imagine we could travel back in time ⏪⌛️to explore the world of bacterial pathogens before humans discovered and industrialised antibiotics

We just did that to study the history of #AMR spread @science.org
doi.org/10.1126/scie...

If you like time travel & biology, this 🧵is for you👇