Development of an antimicrobial resistance plasmid transfer gene database for enteric bacteria

Suad Algarni; Steven L Foley; Hailin Tang; Shaohua Zhao; Dereje D Gudeta; Bijay K Khajanchi; Steven C Ricke; Jing Han

doi:10.3389/fbinf.2023.1279359

Development of an antimicrobial resistance plasmid transfer gene database for enteric bacteria

Front Bioinform. 2023 Nov 14:3:1279359. doi: 10.3389/fbinf.2023.1279359. eCollection 2023.

Authors

Suad Algarni^{1

2}, Steven L Foley¹, Hailin Tang³, Shaohua Zhao⁴, Dereje D Gudeta¹, Bijay K Khajanchi¹, Steven C Ricke⁵, Jing Han¹

Affiliations

¹ Division of Microbiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, United States.
² Cellular and Molecular Biology Graduate Program, University of Arkansas, Fayetteville, AR, United States.
³ Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, United States.
⁴ Office of Applied Science, Center for Veterinary Medicine, Food and Drug Administration, Laurel, MD, United States.
⁵ Meat Science and Animal Biologics Discovery Program, Animal and Dairy Sciences Department, University of Wisconsin, Madison, WI, United States.

Abstract

Introduction: Type IV secretion systems (T4SSs) are integral parts of the conjugation process in enteric bacteria. These secretion systems are encoded within the transfer (tra) regions of plasmids, including those that harbor antimicrobial resistance (AMR) genes. The conjugal transfer of resistance plasmids can lead to the dissemination of AMR among bacterial populations. Methods: To facilitate the analyses of the conjugation-associated genes, transfer related genes associated with key groups of AMR plasmids were identified, extracted from GenBank and used to generate a plasmid transfer gene dataset that is part of the Virulence and Plasmid Transfer Factor Database at FDA, serving as the foundation for computational tools for the comparison of the conjugal transfer genes. To assess the genetic feature of the transfer gene database, genes/proteins of the same name (e.g., traI/TraI) or predicted function (VirD4 ATPase homologs) were compared across the different plasmid types to assess sequence diversity. Two analyses tools, the Plasmid Transfer Factor Profile Assessment and Plasmid Transfer Factor Comparison tools, were developed to evaluate the transfer genes located on plasmids and to facilitate the comparison of plasmids from multiple sequence files. To assess the database and associated tools, plasmid, and whole genome sequencing (WGS) data were extracted from GenBank and previous WGS experiments in our lab and assessed using the analysis tools. Results: Overall, the plasmid transfer database and associated tools proved to be very useful for evaluating the different plasmid types, their association with T4SSs, and increased our understanding how conjugative plasmids contribute to the dissemination of AMR genes.

Keywords: Enterobacteriaceae; WGS analyses tools; conjugation; database; plasmids; transfer genes.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was supported by the National Center for Toxicological Research and U.S. Food and Drug Administration. DG was supported in part by an appointment to the Research Participation Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration.