Aaron Behr

All Publications

• Transposable elements are driving rapid adaptation of Enterococcus faecium. Nature Grieshop, M. P., Behr, A. A., Bowden, S., Lin, J. D., Molari, M., Reynolds, G. Z., Brooks, E. F., Doyle, B., Moore, A. A., Rodriguez-Nava, G., Salinas, J. L., Banaei, N., Bhatt, A. S. 2026

  Abstract

  Bacterial pathogens adapt rapidly to clinical and within-host selective pressures1. Insertion sequences (IS) are transposable elements that can contribute to pathogenic adaptation2, but their activity and consequences in contemporary clinical populations are not well characterized. Here, combining large-scale genomic surveys with long-read sequencing of clinical isolates and longitudinal gut metagenomes, we quantify pathogen IS dynamics from global patterns to within-host evolution. Across 19,485 publicly available high-contiguity ESKAPEE pathogen genomes, Enterococcus faecium genomes are the most IS dense, dominated by replicative ISL3 family elements, which have proliferated in clinical lineages over the past 30 years. We find extensive chromosomal structural variation, largely involving ISL3, within a new single-hospital collection of bloodstream isolates. Long-read metagenomic sequencing of 28 longitudinal stool samples from 12 haematopoietic cell transplantation (HCT) recipients demonstrates within-host IS dynamics and their regulatory consequences. In one patient, an ISL3 insertion upstream of a folate transporter formed a strong promoter, increasing transcription and improving relative fitness under folate limitation. Enhanced folate scavenging may enable E. faecium to thrive in the setting of microbiome collapse, which is common in HCT and other critically ill patients3. Together, these results show that a recent ISL3 expansion is driving rapid evolution in healthcare-associated E. faecium, with consequences for its metabolic fitness that may help explain its increasing clinical burden. Several other pathogens also show elevated IS loads in our survey, which suggests that IS expansion-mediated evolution might be more broadly relevant.

  View details for DOI 10.1038/s41586-026-10373-2

  View details for PubMedID 42020750

  View details for PubMedCentralID 7190074

• 'Jumping genes' help a bacterium that causes hospital infections to adapt quickly NATURE Behr, A. A., Grieshop, M. P. 2026

  View details for DOI 10.1038/d41586-026-01274-5

  View details for Web of Science ID 001747101200001

  View details for PubMedID 42020586

• Impact of stopping contact precautions on vanA plasmid transmission, Northern California, 2021-2023. Antimicrobial stewardship & healthcare epidemiology : ASHE Rodriguez-Nava, G., Grieshop, M. P., Zulli, A., Behr, A. A., Miranti, E., Tariq, W., Viana-Cardenas, E. P., Pincus, N., Banaei, N., Sampson, M., Bhatt, A. S., Salinas, J. L. 2026; 6 (1): e140

  Abstract

  To evaluate the impact of discontinuing contact precautions for vancomycin-resistant enterococci (VRE) on strain and plasmid transmission using long-read whole-genome sequencing (WGS).Before-after trial of adults with Enterococcus bloodstream infections pre-(Jan-Oct 2021) and post-(Oct-Dec 2021 and Jan-Oct 2023) discontinuation of contact precautions for VRE infections.Quaternary referral and transplant academic medical center.Hospitalized adults (≥18 yr) with E. faecalis or E. faecium bacteremia.Classical epidemiology identified potential transmissions via shared unit exposure within a 14-day window. Blood culture isolates underwent long-read WGS to assess strain and vanA plasmid relatedness. Clonal transmission was defined as <20 single-nucleotide polymorphisms. Plasmid similarity was assessed with Mash distance.Among 288 isolates from 202 patients, there was no significant difference in possible epidemiologic transmissions pre-versus postdiscontinuation (9.5% vs 8.1%; P = .679). Genomic analysis identified four clonal transmission events, two of which occurred postdiscontinuation. Among 70 vanA plasmids from 54 patients, 38 highly related plasmids formed a low-diversity cluster. The proportion of cluster plasmids was not significantly different between periods (47% vs 60%; P = .267). Postdiscontinuation, vanA-positive E. faecium ST117 was more prevalent (22/44 vs 53/75; P = .024).Discontinuation of contact precautions for VRE was not associated with increased transmission of enterococci or vanA plasmids in bloodstream infections. Transmission patterns remained largely stable, though the postdiscontinuation period showed increased prevalence of the dominant E. faecium ST117. These findings suggest limited impact of contact precautions on VRE transmission.

  View details for DOI 10.1017/ash.2026.10392

  View details for PubMedID 42130491

  View details for PubMedCentralID PMC13162067

• Replicative selfish genetic elements are driving rapid pathogenic adaptation of Enterococcus faecium. bioRxiv : the preprint server for biology Grieshop, M. P., Behr, A. A., Bowden, S., Lin, J. D., Molari, M., Reynolds, G. Z., Brooks, E. F., Doyle, B., Rodriguez-Nava, G., Salinas, J. L., Banaei, N., Bhatt, A. S. 2025

  Abstract

  Understanding how healthcare-associated pathogens adapt in clinical environments can inform strategies to reduce their burden. Here, we investigate the hypothesis that insertion sequences (IS), prokaryotic transposable elements, are a dominant mediator of rapid genomic evolution in healthcare-associated pathogens. Among 28,207 publicly available pathogen genomes, we find high copy numbers of the replicative ISL3 family in healthcare-associated Enterococcus faecium, Streptococcus pneumoniae and Staphylococcus aureus. In E. faecium, the ESKAPE pathogen with the highest IS density, we find that ISL3 proliferation has increased in the last 30 years. To enable better identification of structural variants, we long read-sequenced a new, single hospital collection of 282 Enterococcal infection isolates collected over three years. In these samples, we observed extensive, ongoing structural variation of the E. faecium genome, largely mediated by active replicative ISL3 elements. To determine if ISL3 is actively replicating in clinical timescales in its natural, gut microbiome reservoir, we long read-sequenced a collection of 28 longitudinal stool samples from patients undergoing hematopoietic cell transplantation, whose gut microbiomes were dominated by E. faecium. We found up to six structural variants of a given E. faecium strain within a single stool sample. Examining longitudinal samples from one individual in further detail, we find ISL3 elements can replicate and move to specific positions with profound regulatory effects on neighboring gene expression. In particular, we identify an ISL3 element that upon insertion replaces an imperfect -35 promoter sequence at a folT gene locus with a perfect -35 sequence, which leads to substantial upregulation of expression of folT, driving highly effective folate scavenging. As a known folate auxotroph, E. faecium depends on other members of the microbiota or diet to supply folate. Enhanced folate scavenging may enable E. faecium to thrive in the setting of microbiome collapse that is common in HCT and other critically ill patients. Together, ISL3 expansion has enabled E. faecium to rapidly evolve in healthcare settings, and this likely contributes to its metabolic fitness and may strongly influence its ongoing trajectory of genomic evolution.

  View details for DOI 10.1101/2025.03.16.643550

  View details for PubMedID 40161577

  View details for PubMedCentralID PMC11952509

• pong: fast analysis and visualization of latent clusters in population genetic data. Bioinformatics (Oxford, England) Behr, A. A., Liu, K. Z., Liu-Fang, G., Nakka, P., Ramachandran, S. 2016; 32 (18): 2817-23

  Abstract

  A series of methods in population genetics use multilocus genotype data to assign individuals membership in latent clusters. These methods belong to a broad class of mixed-membership models, such as latent Dirichlet allocation used to analyze text corpora. Inference from mixed-membership models can produce different output matrices when repeatedly applied to the same inputs, and the number of latent clusters is a parameter that is often varied in the analysis pipeline. For these reasons, quantifying, visualizing, and annotating the output from mixed-membership models are bottlenecks for investigators across multiple disciplines from ecology to text data mining.We introduce pong, a network-graphical approach for analyzing and visualizing membership in latent clusters with a native interactive D3.js visualization. pong leverages efficient algorithms for solving the Assignment Problem to dramatically reduce runtime while increasing accuracy compared with other methods that process output from mixed-membership models. We apply pong to 225 705 unlinked genome-wide single-nucleotide variants from 2426 unrelated individuals in the 1000 Genomes Project, and identify previously overlooked aspects of global human population structure. We show that pong outpaces current solutions by more than an order of magnitude in runtime while providing a customizable and interactive visualization of population structure that is more accurate than those produced by current tools.pong is freely available and can be installed using the Python package management system pip. pong's source code is available at https://github.com/abehr/pongaaron_behr@alumni.brown.edu or sramachandran@brown.eduSupplementary data are available at Bioinformatics online.

  View details for DOI 10.1093/bioinformatics/btw327

  View details for PubMedID 27283948

  View details for PubMedCentralID PMC5018373