Investigation of the role of transposons in the genomic structure of prokaryotes with a focus on the diversity, mobilization, and dissemination of resistance genes in environmental, hospital, and production animal samples

• Grant number: 23/08702-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2024
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Alessandro de Mello Varani
• Grantee: Anelise Stella Ballaben
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil

Abstract

Antimicrobial resistance (AMR) is a serious threat to global public health, recognized by major regulatory, economic, and political bodies, including the International Monetary Fund, the World Health Organization (WHO), the World Bank, and the G8, as one of the greatest global health challenges of the 21st century. The ability of resistance genes to spread through mobile genetic elements (MGE) makes it even harder to contain AMR, as the capture, accumulation, and dissemination of these genes are largely due to the action of these elements. Over the past decades, a wide variety of prokaryotic MGEs has been identified, including different plasmids, insertion sequences (IS), transposons (Tn), integrons (In), and genomic islands (IG). These elements are capable of capturing passenger genes related to AMR and others associated with the emergence of virulence and pathogenicity. When linked to conjugative plasmids, IS, Tn, and their associated integrons and IG, they contribute significantly not only to the reorganization of the genome, impacting functionally but also to the propagation of AMR and other genes that can confer adaptive traits. Therefore, cataloging, analyzing, and understanding the mechanisms of action of these elements is an indispensable step in the fight to deal with the public health crisis caused by AMR, also aiding in the elucidation of processes involved in the evolution of genomic structure and the emergence of virulence and pathogenicity. In this sense, we will use the protocols established by the TnCentral (https://tncentral.ncc.unesp.br) and ISfinder (https://isfinder.biotoul.fr/) databases for high-quality identification and annotation of these elements. Thus, this project aims to investigate, through comparative genomics methods using the TnCentral and ISfinder framework and next-generation sequencing, the mechanisms of AMR evolution driven by plasmids, IS, Tn, In, and IG, and their impacts on genomic structure. In particular, we intend to identify new groups of MGEs, reveal their diversity and composition, and propose specific mechanisms involved in the mobilization of clinically important antimicrobial resistance genes. The results obtained by this project may provide insights for future measures and/or interventions in the fight against antimicrobial resistance and reveal the composition and genomic impact caused by these elements. (AU)