Jerónimo Rodríguez-Beltrán

@jerorb.bsky.social

We study Antibiotic Resistance Ecology and Evolution · Ramón y Cajal University Hospital · Madrid · www.evodynamicslab.com

🚨 New preprint with @annadewar.bsky.social 🚨 Do plasmids “ameliorate” towards their hosts? Maybe… We show that the classic plasmid-host GC correlation is confounded by population structure, and argue that plasmid mobility shapes the opportunity for host-associated compositional evolution.

Mobility shapes plasmid GC content evolution

Plasmids are frequently AT-rich relative to their bacterial hosts. Despite this tendency towards lower GC content, plasmid and host chromosome GC content are positively correlated across diverse collections of plasmid-host pairs. However, the evolutionary processes underlying this pattern remain unclear. The classic model of amelioration predicts that horizontally acquired DNA gradually converges on host nucleotide composition. However, because plasmids can repeatedly transfer between bacterial hosts, the opportunity for such host-associated evolution may depend on their transmission dynamics. Using 50,936 plasmid-host pairs from a public sequence database, we found that the apparent global correlation between plasmid and host chromosome GC content was largely driven by differences between bacterial species rather than within species. We therefore accounted for plasmid and host population structure when testing how plasmid mobility shaped host-associated compositional evolution. We compared two contrasting regimes: a population of 3,682 Enterobacterales plasmids distributed across diverse host backgrounds, and six long-term host-associated plasmids from a Rhizobium leguminosarum lineage with INSeq-determined gene essentiality data. In the Enterobacterales population, GC content variation was overwhelmingly explained by plasmid lineage rather than host phylogeny, and conjugative plasmids showed greater similarity to their host chromosomes than mobilisable or non-mobilisable plasmids. In the Rhizobium leguminosarum plasmids, synonymous-site composition was more similar to the host chromosome among genes required across multiple host life stages. Together, these results support a model in which plasmid mobility influences the opportunity for host-associated evolutionary processes to alter nucleotide composition. ### Competing Interest Statement The authors have declared no competing interest. Wellcome Trust, 319534/Z/24/Z St. John's College, University of Oxford, UK

doi.org

🧬 I'm looking for a Researcher (2 years) in Molecular Biology and Antimicrobial Resistance at UiT The ❄️Arctic University of Norway (Tromsø). 🔬 If you have experience building and screening enzyme libraries and characterising the variants that come out, get in touch.

Happy to share that our latest research on the eco-evolutionary dynamics of MDR plasmids and PDPs is now out (open access vAuthor) in The ISME Journal doi.org/10.1093/isme... Here, we explored how plasmid-dependent phages (PDPs) act as a selective pressure against the spread of multidrug resistance

Eco-evolutionary responses to plasmid-dependent phage constrain the spread of multidrug resistance plasmids

Abstract. Phage therapy offers a promising alternative to antibiotics for treating multidrug-resistant infections. Plasmid-dependent phages (PDPs) are part

doi.org

@biorxiv-microbiol.bsky.social Who knew ParB-CTPase fold can kill!!! A protein fold best known for segregating chromosomes…can be transformed into a potent antibacterial toxin in some plant and animal pathogens. www.biorxiv.org/content/10.6...

Repurposing a chromosome segregation ParB-CTPase fold into an ATPase toxin for contact-dependent growth inhibition in plant and animal pathogens

Bacterial competition drives the evolution of antibacterial mechanisms, yet how new activities arise remains poorly understood. A major route to innovation is the reuse of pre-existing genetic systems, whereby conserved protein modules are repurposed in new biological contexts to generate new capabilities. Here, we show that the ParB-CTPase fold, a conserved nucleotide-binding module best known for its role in chromosome segregation, can be functionally repurposed as an antibacterial toxin. We identify ToxB, a ParB-like domain embedded within the polymorphic toxin region of contact-dependent inhibition systems and show that it functions as a potent antibacterial effector. Structural and biochemical analyses reveal that ToxB retains the core architecture of the ParB-CTPase fold but lacks DNA-binding capability and preferentially binds ATP. This shift in nucleotide specificity underpins a distinct mode of action, in which ATP binding and hydrolysis trigger rapid nucleoid compaction, chromosome segregation defects, oxidative stress, cell chaining, and ultimately cell lysis. ToxB also exhibits toxic activity in plant cells, suggesting that it targets conserved cellular processes. Together, these findings provide direct experimental evidence that the ParB-NTPase fold is biologically versatile and can be repurposed for biological roles fundamentally distinct from its ancestral function in DNA segregation. ### Competing Interest Statement The authors have declared no competing interest. Wellcome Trust, https://ror.org/029chgv08, 221776/Z/2/Z, 227755/Z/23/Z Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/X01097X/1 Diamond Light Source, MX32728

biorxiv.org