Jordan Lin

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

• A bacterial toxin-antitoxin system involved in an unusual response to genotoxic stress. EMBO reports Lin, J. D., Nicholson, B., Ensminger, A. W. 2025

  Abstract

  To contend with environmental challenges, bacteria have evolved numerous stress response pathways. A notable example is the adoption of a dormant state called persistence, whereby cells reversibly restrict their growth and await favorable conditions. The genetics of persistence remain poorly understood, and genes called toxin-antitoxin (TA) systems have controversially been implicated in this phenotype. To examine their role in persistence, we construct a pan-TA deletion strain of the bacterial pathogen Legionella pneumophila and test its capacity to survive diverse stresses. We identify a single predicted TA system, GndRX, that under genotoxic stress conditions leads to cell death rather than promoting survival, whereas ∆gndRX cells adopt a viable but nonculturable state. Strikingly, this enhanced survival is conferred to wild-type cells in a contact-dependent manner during co-culture. Despite having homology to other TA systems, GndRX displays non-canonical activity, and we hypothesize that it has undergone functional domestication by the cell. Overall, our work reveals both a new physiological function for TA systems in bacteria as well as a heretofore undescribed phenomenon of contact-dependent survival within persister cells.

  View details for DOI 10.1038/s44319-025-00545-y

  View details for PubMedID 40825874

  View details for PubMedCentralID 7136161

• Functional diversificationdiversification despite structural congruence in the HipBST toxin-antitoxin system of Legionella pneumophila MBIO Lin, J. D., Stogios, P. J., Abe, K. T., Wang, A., MacPherson, J., Skarina, T., Gingras, A., Savchenko, A., Ensminger, A. W. 2023; 14 (5): e0151023

  Abstract

  Toxin-antitoxin (TA) systems are parasitic genetic elements found in almost all bacterial genomes. They are exchanged horizontally between cells and are typically poorly conserved across closely related strains and species. Here, we report the characterization of a tripartite TA system in the bacterial pathogen Legionella pneumophila that is highly conserved across Legionella species genomes. This system (denoted HipBSTLp) is a distant homolog of the recently discovered split-HipA system in Escherichia coli (HipBSTEc). We present bioinformatic, molecular, and structural analyses of the divergence between these two systems and the functionality of this newly described TA system family. Furthermore, we provide evidence to refute previous claims that the toxin in this system (HipTLp) possesses bifunctionality as an L. pneumophila virulence protein. Overall, this work expands our understanding of the split-HipA system architecture and illustrates the potential for undiscovered biology in these abundant genetic elements.

  View details for DOI 10.1128/mbio.01510-23

  View details for Web of Science ID 001191200600030

  View details for PubMedID 37819088

  View details for PubMedCentralID PMC10653801

• Diverse Bacteria Utilize Alginate Within the Microbiome of the Giant Kelp <i>Macrocystis pyrifera</i> FRONTIERS IN MICROBIOLOGY Lin, J. D., Lemay, M. A., Parfrey, L. W. 2018; 9: 1914

  Abstract

  Bacteria are integral to marine carbon cycling. They transfer organic carbon to higher trophic levels and remineralise it into inorganic forms. Kelp forests are among the most productive ecosystems within the global oceans, yet the diversity and metabolic capacity of bacteria that transform kelp carbon is poorly understood. Here, we use 16S amplicon and metagenomic shotgun sequencing to survey bacterial communities associated with the surfaces of the giant kelp Macrocystis pyrifera and assess the capacity of these bacteria for carbohydrate metabolism. We find that Macrocystis-associated communities are distinct from the water column, and that they become more diverse and shift in composition with blade depth, which is a proxy for tissue age. These patterns are also observed in metagenomic functional profiles, though the broader functional groups-carbohydrate active enzyme families-are largely consistent across samples and depths. Additionally, we assayed more than 250 isolates cultured from Macrocystis blades and the surrounding water column for the ability to utilize alginate, the primary polysaccharide in Macrocystis tissue. The majority of cultured bacteria (66%) demonstrated this capacity; we find that alginate utilization is patchily distributed across diverse genera in the Bacteroidetes and Proteobacteria, yet can also vary between isolates with identical 16S rRNA sequences. The genes encoding enzymes involved in alginate metabolism were detected in metagenomic data across taxonomically diverse bacterial communities, further indicating this capacity is likely widespread amongst bacteria in kelp forests. Overall, the M. pyrifera epibiota shifts across a depth gradient, demonstrating a connection between bacterial assemblage and host tissue state.

  View details for DOI 10.3389/fmicb.2018.01914

  View details for Web of Science ID 000442106400001

  View details for PubMedID 30177919

  View details for PubMedCentralID PMC6110156