Alvaro San Millan

New preprint on the limits of detecting higher-order interactions in microbial communities.
www.biorxiv.org/content/10.6...
We find that the dominance of additive and pairwise interactions on community function may not reflect biological simplicity, but fundamental limits of statistical detection.

Excited to share our latest work! 📝

We measured the fitness effect of 136 AMR genes and found that many are neutral or even beneficial without selection. 🤯🧬

Oxygen availability can flip their fitness and our stochastic model indicates that oxygen fluctuations help maintain them.

Learn more 👇🏼

New preprint out on bioRxiv!

www.biorxiv.org/content/10.6...

Can conjugative plasmids be used to control plasmid and pathogen spread?

Follow me down the rabbit hole that led to this story 🧵

Great news!! Really looking forward to starting this collaboration

Co-occurrence is associated with horizontal gene transfer across marine bacteria independent of phylogeny Abstract. Understanding the drivers and consequences of horizontal gene transfer (HGT) is a key goal of microbial evolution research. Although co-occurring

Now out & nicely formatted in @isme-microbes.bsky.social

A big analysis of ocean genomes & metagenomes co-led by former postdocs, now PIs, @gmdouglas.bsky.social & @cyanophage.bsky.social along with co-PIs @lbobay.bsky.social & Samuel Chaffron.

A few highlights... 🧵 (1/n)

doi.org/10.1093/isme...

So great to finally have such a clear answer to this question!! Well done guys!

Congratulations!!!

PlasAnn: a curated plasmid-specific database and annotation pipeline for standardized gene and function analysis Abstract. Conjugative plasmids are key drivers of bacterial adaptation, enabling the horizontal transfer of accessory genes within and across diverse micro

Big week: welcomed a new baby boy Harris Lopatkin, AND our PlasAnn paper is finally out: academic.oup.com/nar/article/... (obviously the first more important than the second 🥰). Currently on leave but if anyone has the need to annotate large plasmids, go check it out!

Plasmid mutation rates scale with copy number | PNAS Plasmids are extrachromosomal DNA molecules that spread by horizontal transfer and shape bacterial evolution. Plasmids are typically present at mul...

New paper out in PNAS!!! 🎉

Do more plasmid copies mean faster evolution?

🧵 Dive into the story

www.pnas.org/doi/10.1073/...

New paper out in @pnas.org, and it made the cover! 👁️

We represent plasmids as circles and mutations as dots, resembling an eye, because in this paper we literally 𝑤𝑎𝑡𝑐ℎ plasmids evolve.

‼️Check Paula’s 🧵 and the paper👇

𝗣𝗹𝗮𝘀𝗺𝗶𝗱 𝗺𝘂𝘁𝗮𝘁𝗶𝗼𝗻 𝗿𝗮𝘁𝗲𝘀 𝘀𝗰𝗮𝗹𝗲 𝘄𝗶𝘁𝗵 𝗰𝗼𝗽𝘆 𝗻𝘂𝗺𝗯𝗲𝗿
www.pnas.org/doi/10.1073/...

Novel genes arise from genomic deletions across the bacterial tree of life https://www.biorxiv.org/content/10.64898/2026.01.05.697752v1

Growth control as a central regulator for tuning the cellular context The cellular context interacts with genetic circuits, decisively defining their performance. However, contextual dependencies (the interplay between the host and the circuit) are often difficult to en...

Preprint out! By controlling growth, via RNAP, we control the entire cellular machinery, and tune the cellular context into distinct, stable states. See how NOT gates behave! Kudos to @angeles-hg.bsky.social and @mirobueno.bsky.social

🔗https://www.biorxiv.org/content/10.64898/2025.12.19.695408v1

Plasmid streamlining drives the extinction of antibiotic resistance plasmids under selection for horizontal transmission Conjugative plasmids play an important role in the spread of antimicrobial resistance (AMR) genes among pathogenic bacteria. This study shows that AMR loss in evolving populations is associated with t...

Our story on plasmid streamlining is now published in PLoS Biology! With @andrewmatthews.bsky.social and @sonjalehtinen.bsky.social
#MicroSky #Mevosky
journals.plos.org/plosbiology/...

2 out of 3 😉

Last week, we hosted the XXXIII CNB Scientific Workshop.

We are delighted to announce this year’s award winners:

🏆 Best Postdoctoral Talk: Alicia Calvo-Villamañán
🏆 Best PhD Talk: Silvia López Borrego
🏆 Best Poster: Jorge Sastre Domínguez

Congratulations to all!

#CNB_CSIC

A pleasure and an honour to have received this prestigious grant with my admired colleagues and friends @sanmillan.bsky.social and @asanchezlab.bsky.social . More about AMR under plasmid lens!. My sincere gratitude to @caixaresearch.bsky.social

@microryc.bsky.social @esgem-sg.bsky.social

Intracellular competition shapes plasmid population dynamics From populations of multicellular organisms to selfish genetic elements, conflicts between levels of biological organization are central to evolution. Plasmids are extrachromosomal, self-replicating g...

Hot off the press! Our latest paper led by @fernpizza.bsky.social, understanding how plasmids evolve inside cells. These small, self-replicating DNA circles live inside bacteria and carry antibiotic resistance genes, but also compete with one another to replicate. 1/
www.science.org/doi/10.1126/...

👏 Dos proyectos del #CNB seleccionados en la convocatoria de Investigación en Salud 2025 de la @caixaresearch.bsky.social

Ambos abordan un gran reto global: la resistencia a los antimicrobianos.

#HealthResearch #FundaciónlaCaixa
@sanmillan.bsky.social @jaescudero.bsky.social

f.mtr.cool/jejatlbssz

Really honoured to have received this amazing grant together with my incredible colleagues @asanchezlab.bsky.social and @tmcoque.bsky.social

1/ Antibiotic resistance causes ➕ than 1 M deaths each year and understanding why this happens is key to stopping it.

With #HealthResearch support, @sanmillan.bsky.social is investigating how different plasmids (DNA fragments) coexist in bacteria and confer resistance.

https://tinyurl.com/3bysv6cr

Bacterial warfare is associated with virulence and antimicrobial resistance - Nature Communications Bacteria employ a range of competition systems that deliver toxins to inhibit competing strains. This study shows that these systems are particularly important for the ecology of virulent and antibiot...

So happy to share this! Bacteriocins were first discovered over 100 years ago, but what do they actually do? We look at >1000 bacteriocin plasmids and find links to virulence and antimicrobial resistance, and frequent bacteriocin sharing in Enterobacteriaceae.
www.nature.com/articles/s41...

New preprint out! 📣🚨

We found that loss-of-function mutations in the carbapenem entry porin OprD of Pseudomonas aeruginosa do more than confer #AntibioticResistance: they reshape the bacterial membrane and interaction with the host, enhancing epithelial colonization capacity 🦠

#Microsky

Massively parallel interrogation of the fitness of natural variants in ancient signaling pathways reveals pervasive local adaptation The nature of standing genetic variation remains a central debate in population genetics, with differing perspectives on whether common variants are almost always neutral as suggested by neutral and n...

One of the most exciting works of my career, years in the making. We used high-throughput precision genome editing to test the fitness effects of thousands of natural variants. Our findings challenge the long-held assumption that common variants are inconsequential.

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

Non-conjugative plasmids limit their mobility to persist in nature Sabnis et al. explain why non-conjugative plasmids move at a low rate in nature. While increased mobility can easily evolve by incorporating phage DNA into plasmids, this is disadvantageous because it...

✨New paper from @jrpenades.bsky.social and @sanmillan.bsky.social labs. We found that non-conjugative plasmids 🧬 tend to have low mobility to promote functional diversity ⚔️💊 in bacterial communities🦠🦠.
Brilliant work by Akshay, @asantoslopez.bsky.social and others.

www.cell.com/cell-reports...

Non-conjugative plasmids limit their mobility to persist in nature Sabnis et al. explain why non-conjugative plasmids move at a low rate in nature. While increased mobility can easily evolve by incorporating phage DNA into plasmids, this is disadvantageous because it...

New paper with my (amazing) friend and mentor @jrpenades.bsky.social
Really looking forward to see what plasmid aficionados think of this one!!
With @asantoslopez.bsky.social @wfigueroac3.bsky.social Akshay Sabins and others
www.cell.com/cell-reports...

The assembly of a hybrid type IV secretion system by a Crohn’s disease-associated Escherichia coli strain - Nature Communications Adherent-invasive strains of E. coli are commonly isolated from patients with Crohn’s disease. Here, the authors show that an AIEC harbours a hybrid Type IV secretion system (T4SS) that mediates pilin...

New paper just out from #OurImperial @tcostalab.bsky.social

The assembly of a hybrid type IV secretion system by a Crohn’s disease-associated Escherichia coli strain.

www.nature.com/articles/s41...

Dissecting pOXA-48 fitness effects in clinical Enterobacterales using plasmid-wide CRISPRi screens - Nature Communications This study investigates the effects of the carbapenem resistance plasmid pOXA-48 in clinical enterobacteria. Using CRISPRi screens, the authors revealed that the carbapenemase OXA-48 has a role in the plasmid-associated fitness costs.

Dissecting the fitness effects of a carbapenem resistance plasmid in clinical Enterobacterales using plasmid-wide CRISPRi screens

@aliciapcv.bsky.social @jorgesastred.bsky.social @sanmillan.bsky.social @cnb-csic.bsky.social

#bacteria #plasmids

DYK most P. aeruginosa carry filamentous phage(s) that don't need to kill the cell to reproduce?

We 👉🏻@nanamikubota.bsky.social show that these Pf phages can go ROGUE.

"Filamentous cheater phages drive bacterial and phage populations to lower fitness"

🔗 authors.elsevier.com/c/1lt5I3QW8S...

Gracias, Pedro!

I was there!!