Pesonen, H. | Search bioRxiv

bioRxiv2026

Rapid gene exchange explains differences in bacterial pangenome structure

The size and diversity of bacterial gene repertoires, known as pangenomes, vary widely across species. The evolutionary forces driving the maintenance of pangenomes is an open topic of debate, with contradictory theories suggesting that pangenomes exist as a result of neutral evolution, with all genes gained and lost at random, or that all genes provide a fitness benefit to the host and are maintained by positive selection. Modelling of pangenome dynamics has provided insight into how gene exchange explains observed gene frequency distributions, and stands as the only means of jointly inferring contributions of individual gene selection effects and mobility on the maintenance of pangenomes. However, previous modelling studies have not included both gene-level selection and mobility, and do not consider broadly sampled genome datasets for many species. To differentiate neutral and selective forces maintaining pangenomes, we developed a mechanistic model of gene-level evolution, Pansim, and a scalable model fitting framework, PopPUNK-mod. Together, these tools leverage rapid genome distance calculation to fit models of pangenome dynamics to datasets containing hundreds of thousands of genomes. We used this framework to compare the pangenome dynamics of over 400 different bacterial species, using over 600,000 genomes. We find that diversity in pangenome characteristics between species is driven predominantly by variation in the number of rapidly exchanged genes, while the rate of exchange of remaining genes is conserved. We find that bacterial phylogeny, rather than ecology, correlates with pangenome dynamics. We express that pan-species gene-level analyses are now needed to understand selection across accessory genes. Our work highlights the importance of gene exchange rate differences in governing differences in pangenome characteristics between species.

bioinformatics↗

bioRxiv2024

Basic reproduction number for pandemic Escherichia coli clones is comparable to typical pandemic viruses

Extra-intestinal pathogenic Escherichia coli (ExPEC) ubiquitously colonize the human gut and represent clinically the most significant bacterial species causing urinary tract infections and bacteremia in addition to contributing to meningitis in neonates. During the last two decades, new E. coli multi-drug resistant clones such as ST131, particularly its clades C1 and C2, have spread globally, as has their generally less resistant sister clade ST131-A. Phylodynamic coalescent modeling has indicated exponential growth in the populations corresponding to these clades during the early 2000s. However, it remains unknown how their transmission dynamics compare to viral epidemics and pandemics in terms of key epidemiological quantities such as the basic reproduction number (R0). Estimation of R0 for opportunistic pathogenic bacteria poses a difficult challenge compared to viruses causing acute infections, since data on E. coli infections accumulate with a much longer delay, even in the most advanced public health reporting systems. Here, we developed a compartmental model for asymptomatic gut colonization and onward transmission coupled with a stochastic epidemiological observation model for bacteremia and fitted the model to annual Norwegian national E. coli disease surveillance and bacterial population genomics data. Approximate Bayesian Computation leveraged by the ELFI software package was used to infer R0 for the pandemic ST131 clades. The resulting R0 estimates for ST131-A, ST131-C1 and ST131-C2 were 1.47 (1.31-1.60), 1.18 (1.12-1.20) and 1.13 (1.08-1.20), respectively, indicating that the ST131-A transmission potential can be even comparable to pandemic influenza viruses, such as H1N1. The significantly lower transmissibility of ST131-C1 and ST131-C2 suggests that their global dissemination has been aided by antibiotic selection pressure and that they may be more effectively transmitted through healthcare facilities instead of primarily community-driven transmission. In summary our results provide a fundamental advance in understanding the relative transmissibility of these opportunistic pathogens and that it can vary markedly even between very closely related E. coli.

microbiology↗