Authors:

Sakesh Andhavarapu

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About Paper:

Antimicrobial resistance (AMR) is a top global public health and ongoing threat that was associated with 4.71 million deaths in 2021, including 1.14 million deaths directly attributed to AMR. As the effectiveness of traditional antibiotics declines and new antibiotic development remains slow, patients undergoing long-term or repeated antibiotic treatments, such as those with recurrent Clostridium difficile infection (rCDI) or colonization by multidrug-resistant bacteria (MDRB), face increasingly limited treatment options. In these high-risk populations, when conventional therapies fail, microbiome-based strategies such as Fecal Microbiota Transplantation (FMT) offer an alternative by restoring microbial balance either independently or alongside antibiotics. Although research has been conducted to investigate the clinical outcomes of FMT, the extent to which it impacts genetic mechanisms of resistance, including AMR genes (ARGs) and mobile genetic elements (MGEs) patterns remains insufficiently characterized. Critically, there is a lack of comprehensive, temporally resolved network analyses that examine how FMT influences persistence, reduction, or transfer of ARGs that have innate transfer potential due to their association with MGEs over time. To investigate these patterns, 263 publicly available metagenomic samples from FMT donors and recipients (Pre-FMT and Post-FMT) that span rCDI , MDRB infections, and melanoma were analyzed. Resistome and mobilome count matrices were produced utilizing gene classification pipelines. A novel Network-based framework has been implemented to analyze and visualize the temporal modifications of ARGs and MGEs in the microbiome. In this network, nodes represent ARGs or MGE mechanisms, annotated by their source origin (donor or recipient). Edges represent temporal shifts in abundance or co-localization relationships, encompassing longitudinal dynamics and potential genomic ARG-MGE links. The most significant changes observed were the emergence of 4,359 new intragenomic colocalizations from unknown sources and the disappearance of 4,564 pre-existing ones following the FMT procedure. Additionally, our results show 130 instances of transfer from the donor to † Presenting Undergrad Author; ‡ Contributing Undergrad Author; * Undergrad Acknowledgment the patient and the persistence of 386 colocalizations that were present in the patient before and after treatment. Only 19 colocalizations were found to persist across all three stages. By quantifying the distinct colocalization dynamics, these findings can contribute to th Keywords: Antimicrobial Resistance (AMR); Fecal Microbiota Transplantation (FMT); Colocalization; Temporally Network Analyses

Source:

Purdue University / 2025

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Co-authors:

Sakesh Andhavarapu