🦠 ¿Cómo se propagan los genes de resistencia a los antibióticos entre bacterias? @sanmillan.bsky.social (@cnb-csic.bsky.social), investigador de nuestra red, estudia el papel de los plásmidos en la transferencia de estos mecanismos de resistencia. 🔗 https://tinyurl.com/2sefv3rh
Alvaro San Millan
@sanmillan.bsky.social
Plasmid biology, antimicrobial resistance plasmidlab.es
Months (years ?) spent on species-wide screens, over 3.000 PCR reactions and an unbelievable amount of 10-uL tips : I'm glad to introduce the novel TAR family of anti-plasmid defenses ! The war between bacteria and their MGEs is far more complex than we expected ⚔️ Read Xavier's 🧵 for more details !
#microsky New preprint from the lab! Widespread immune systems protect bacteria against conjugative plasmids www.biorxiv.org/content/10.6... Kudos to the extremely talented lead author Ludovic Poiré! Key contributions by @francoisrousset.bsky.social and also help from C. Lesterlin/TacC lab. 🧵⬇️
New #microsky#AMR Perspective paper with @penamiller.bsky.social rdcu.be/fqBJo ANTIBIOTIC RESISTANCE (IE MIC) AND TOLERANCE ARE NOT BACTERIAL TRAITS! Please read on if you want an explanation for this provocative claim.
Beyond resistance and tolerance: rethinking evolutionary responses to antibiotics from the perspective of individual bacterial cells
Nature Communications - Beyond resistance and tolerance: rethinking evolutionary responses to antibiotics from the perspective of individual bacterial cells
rdcu.be
👉 Only 2 weeks to go for registrations to the famous ICARe course on #antimicrobials and #resistance in #Annecy, France: www.icarecourse.org Great course, great venue, great networking opportunity with @gdwantibiotics.bsky.social and other huge legends in the field
Interdisciplinary Course on Antibiotics and Resistance
icarecourse.org
Ayer, @sanmillan.bsky.social, investigador en el #CNB_CSIC, participó en #DesayunoDeINNOVACIÓN de @innovaspain.bsky.social en colaboración con Fundación Pfizer. El evento abordó claves para reforzar la transferencia de conocimiento en el sector salud y reforzar el papel de España como referente.
New paper out! 🔈 Genomic Characterization of the RyC collection: 50 Multidrug Resistant Clinical Isolates of Escherichia coli and Klebsiella spp. 50 MDR gut isolates, 2 sequencing platforms, 4 “omes,” and 1 mission: provide a resource to decode AMR and MGE dynamics www.biorxiv.org/content/10.6...
biorxiv.org
🚨 New preprint from the lab! 🚨 We show that multireplicon plasmids are true AMR "jack-of-all-trades": Widespread, highly mobile, broad host-range, and packed with resistance genes. Far from random, they form co-evolving associations driven & 𝘮𝘢𝘪𝘯𝘵𝘢𝘪𝘯𝘦𝘥 by IS elements. See Nacho's thread below!👇👇
Multireplicon plasmids emerge under predictable rules and drive the spread of antimicrobial resistance across bacterial hosts
Plasmids are DNA molecules that replicate independently of the bacterial chromosome and are typically associated with the spread of antimicrobial resistance (AMR) and virulence determinants, among other relevant traits. Fusion events between plasmids generate larger, complex backbones that carry two or more replication systems, known as multireplicon plasmids. Despite decades of study, we are still far from understanding how multireplicon plasmids arise, persist, and shape the evolution of AMR. Here, we analyzed 24,000 non-redundant plasmids across bacterial genera and found that more than 30% of them encoded multiple replicons. Compared to single-replicon plasmids, multireplicon plasmids were larger, were enriched in genes encoding antimicrobial, metal, and biocide resistance as well as virulence factors, and showed higher mobility and a broader host range. We also found that multireplicon assembly is not random. Some replicon pairs repeatedly merge into stable multireplicon plasmids, while other pairs rarely fuse even when they commonly coexist intracellularly. We also show that replicon pairs tend to be localized either in close proximity to one another or on opposite poles of the plasmid. We further highlight that multireplicon plasmids can be broadly classified into two groups: long-term coevolving replicon pairs and transient associations that lack a shared evolutionary history. Finally, we reveal the molecular mechanisms underlying multireplicon formation and highlight the role of insertion sequences in their formation and maintenance. Together, our work sheds light on the abundance, gene content, evolutionary patterns, and formation dynamics of multireplicon plasmids and pinpoints their relevance to bacterial evolution and human health. ### Competing Interest Statement The authors have declared no competing interest. Instituto de Salud Carlos III, https://ror.org/00ca2c886, PI23/01945, PFIS - FI22/00265, Miguel Servet - CP22/00164 European Research Council, https://ror.org/0472cxd90, HorizonGT, 101077809 Fundación Ramón Areces, "Ayudas Fundación Ramón Areces para la realización de Tesis Doctorales en Ciencias de la Vida y de la Materia 2025" Coordenação de Aperfeicoamento de Pessoal de Nível Superior, https://ror.org/00x0ma614, 88881.128025/2025-01
biorxiv.org
What if multireplicon plasmids are not an oddity, but an evolutionary strategy? We found that they are common, more mobile, broader-host-range, and enriched in AMR. Even more interesting: their assembly doesn’t look random. 👀 Paper preprint: www.biorxiv.org/content/10.6... Thread below!🧵👇
Very proud of this work and all the efforts from my team and collaborators on this! You can now use DGRs for in vivo targeted hypermutagenesis in E. coli. We also included some early proof of concept in Yeast thanks to @seth-shipman.bsky.social !
🔈Paper out! We turned the most fascinating phage host-switch mechanism, diversity-generating retroelements, into a programmable mutagenesis tool, DGRec. You can perform targeted hypermutation of any 50-200bp sequence directly in vivo in E. coli www.nature.com/articles/s41...
My main postdoc paper is now out in @natureportfolio.nature.com npj Antimicrobials and Resistance! www.nature.com/articles/s44.... Using flow cytometry, we show that the nucleoside analogues azidothymidine, didanosine, stavudine, and trifluridine reduced transfer of AMR plasmids pCT and pKpQIL (1/3)
Mechanistic insights into plasmid transfer inhibition in Enterobacterales by nucleoside analogues - npj Antimicrobials and Resistance
npj Antimicrobials and Resistance - Mechanistic insights into plasmid transfer inhibition in Enterobacterales by nucleoside analogues
nature.com
En #AGolpeDeBit #RTVE, @sanmillan.bsky.social investigador del #CNB @csic.es habla de este estudio liderado junto a Alfonso Santos López @uam.es y en colaboración con Ayari Fuentes #UNAM_MX centrado en el plásmido pOXA-48 de gran interés clínico 📻 ¡No te lo pierdas! www.rtve.es/play/audios/...
Resistencia a antibióticos: hallada nueva clave en plásmidos
Ponemos el foco en un estudio que identifica un nuevo mecanismo por el que los plásmidos pueden acelerar la aparición de resistencia a los antibióticos
rtve.es
Now out in AEM @asm.org! 🎉🧪 *High school student-isolated mutants 👉🏻 novel genetic causes of biofilm-associated adaptations *We learn how diversity arises quickly and is maintained *EvolvingSTEM enables scalable research in classrooms & promotes scientific literacy journals.asm.org/eprint/FBU9M...
Genetic diversification of Pseudomonas fluorescens maintained by multi-niche selection within biofilms | Applied and Environmental Microbiology
Bacterial biofilms dominate microbial life; however, their evolutionary genetics remain incompletely understood. Extensive replication of biofilm selection experiments by secondary school students can...
journals.asm.org
Sharing the most significant work from my group, led by the @evolvingstem.bsky.social team. Come for the discoveries of how Pseudomonas adapts in biofilms, stay for the story of how they were discovered by thousands of young scientists in grades 9-12. 🧪🧫🧬🧵 www.biorxiv.org/content/10.1...
We are pleased to share our last article rdcu.be/fabhM. It offers the most comprehensive analysis so far of Ab+non-Ab resistance genes in human gut microbiome, using an Indigenous population (low industrialization, chronic Hg exposure from gold mining) 6/6👇
The antimicrobial gut resistome of the Wayampi reveals a shared background of antibiotic and metal resistance genes with industrialized populations, underscoring the “robust-yet-fragile” architecture ...
rdcu.be
Here’s the latest preprint from my work on evolved resistance to Type VI Secretion system (T6SS) weaponry, funded by a @wellcometrust.bsky.social Sir Henry Wellcome Fellowship. So happy to see this out! www.biorxiv.org/content/10.6...
biorxiv.org
New preprint alert!!! 🚀🤓 We are very happy to finally share this with the world — the result of seven years of work and a new tool to study integrons and discover new functions encoded in these bacterial platforms. If you want to know more, here is a thread 🧵 www.biorxiv.org/content/10.6...
biorxiv.org
New #AMR pre-print Combining antibiotics with genotoxins can efficiently suppress bacterial in high throughput experimental models. www.biorxiv.org/content/10.6... Fun collaboration with Nassos Typas lab led by @mulkern.bsky.social
biorxiv.org
Final version of our last paper is out! www.nature.com/articles/s41...
Plasmids promote antimicrobial resistance through insertion sequence-mediated gene inactivation - Nature Microbiology
Inactivation of chromosomal genes through plasmid-encoded IS elements is an extended mechanism of antimicrobial resistance evolution in bacteria.
nature.com
Identifican un nuevo mecanismo utilizado por plásmidos para acelerar la aparición de resistencia a los antibióticos. @sanmillan.bsky.social @uam.es @csic.es Más info en nuestra web: https://f.mtr.cool/pmappovlkt Artículo en: https://f.mtr.cool/yvxpgzaraz @natureportfolio.nature.com @erc.europa.eu
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.
biorxiv.org
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 👇🏼
Fitness effects of antimicrobial resistance genes in changing environments https://www.biorxiv.org/content/10.64898/2026.03.06.710025v1
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 🧵
biorxiv.org
Great news!! Really looking forward to starting this collaboration
I’m incredibly happy to have been awarded an #MSCA Fellowship to join the @sanmillan.bsky.social lab at @csic.es! 🎉🎉 The project includes an exciting secondment at the IRYCIS-RyC hospital! 🏥 Grateful for all the support and the reviewers' recognition of our project in such a competitive call! 🙏
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...
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
doi.org
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!
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
academic.oup.com
New paper out in PNAS!!! 🎉 Do more plasmid copies mean faster evolution? 🧵 Dive into the story www.pnas.org/doi/10.1073/...
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...
pnas.org
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/...
New paper out in PNAS!!! 🎉 Do more plasmid copies mean faster evolution? 🧵 Dive into the story 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
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
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...
biorxiv.org
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/...
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...
journals.plos.org
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