(External) Probing the genetic diversity of integrated mobile elements and their potential role in the spread of antimicrobial resistance

Advisors: Vincent Burrus, Département de biologie, Université de Sherbrooke; Dominic Poulin-Laprade, Agriculture and Agri-Food Canada (UofG faculty to be confirmed)

Proposed co-advisors: Nicole Ricker

The emergence and spread of multi-drug resistant bacterial pathogens have recently been deemed the silent pandemic, as the COVID-19 pandemic has occulted the rising global mortality and morbidity resulting from untreatable bacterial infections. Antimicrobial resistance is a crisis that needs to be addressed at multiple fronts along the One Health continuum. Bacteria from agricultural and marine settings are contributing to human and animal diseases and are increasingly resistant to antibiotics. However, knowledge gaps exist regarding their contribution to AMR in clinical settings. Bacteria exchange multi-drug resistance genes via mobile genetic elements (MGEs) such as conjugative and mobilizable plasmids, integrative and conjugative elements (ICEs), and integrative and mobilizable elements (IMEs). IncC conjugative plasmids and ICEs of the SXT/R391 family are distantly related phylogenetically and functionally. Both play a considerable role in the expansion of antibiotic resistance via their MDR gene cargo but also because they drive the mobilization of MDR-carrying IMEs. We have recently discovered one family of IMEs mobilizable by SXT/R391 ICEs and four distinct families of IMEs mobilizable by IncC plasmids. All these IMEs reside in three integration sites in the genome of Gammaproteobacterial, namely dusA, trmE and yicC. The same three sites are also used as integration for prophages, suggesting that both IMEs and prophages use related integrases. However, we currently have a weak understanding of the diversity of these IMEs and how they relate and interact with each other and with prophages. Assessing the diversity of IMEs and their relationship with prophages is crucial to understanding the evolutionary pathway by which multi-drug resistance IMEs emerge and how they domesticated conjugative plasmids to ensure their own propagation.

This proposed project is at the convergence between academic and governmental initiatives, namely CIHR and the federal Genomics R&D initiatives in AMR. The student will query the Genbank database and in-house bacterial genomes and metagenomes for MGEs inserted at the designated loci using protein sequence anchors and incorporate the resulting MGEs into a new database. The student will annotate the MGEs and search for patterns of protein-coding genes consistent with intra- and inter-cellular mobility. Large-scale protein-protein comparisons and clustering will allow visualization of the associations and relationships between MGEs using network mapping. Finally, the student will search for promoter sequences that are the hallmark of gene expression elicited by IncC plasmids and SXT/R391 ICEs. During the realization of this project, the student will gain expertise in the diversity of mechanisms driving the spread of multi-drug resistance genes and the MGEs that mobilize them. The student will gain competence with the organization, comparison, and visualization of large sequence datasets.

The project can be completed in one semester, yet further development of the analyses to additional integration sites and (meta)genomes from other sectors of the One Health continuum could grant work for a second semester.

This is a remote project.

Knowledge and Skills:

• Basic knowledge of bacterial genetics and mobile genetic elements.
• Python programming, data visualization and statistical analysis.