Functional enrichment of integrons: Facilitators of antimicrobial resistance and niche adaptation

Timothy M Ghaly; Vaheesan Rajabal; Anahit Penesyan; Nicholas V Coleman; Ian T Paulsen; Michael R Gillings; Sasha G Tetu

doi:10.1016/j.isci.2023.108301

Functional enrichment of integrons: Facilitators of antimicrobial resistance and niche adaptation

iScience. 2023 Oct 24;26(11):108301. doi: 10.1016/j.isci.2023.108301. eCollection 2023 Nov 17.

Authors

Timothy M Ghaly¹, Vaheesan Rajabal^{1

2}, Anahit Penesyan^{1

2}, Nicholas V Coleman¹, Ian T Paulsen^{1

2}, Michael R Gillings^{1

2}, Sasha G Tetu^{1

2}

Affiliations

¹ School of Natural Sciences, Macquarie University, New South Wales 2109, Australia.
² ARC Centre of Excellence in Synthetic Biology, Macquarie University, New South Wales 2109, Australia.

Abstract

Integrons are genetic elements, found among diverse bacteria and archaea, that capture and rearrange gene cassettes to rapidly generate genetic diversity and drive adaptation. Despite their broad taxonomic and geographic prevalence, and their role in microbial adaptation, the functions of gene cassettes remain poorly characterized. Here, using a combination of bioinformatic and experimental analyses, we examined the functional diversity of gene cassettes from different environments. We find that cassettes encode diverse antimicrobial resistance (AMR) determinants, including those conferring resistance to antibiotics currently in the developmental pipeline. Further, we find a subset of cassette functions is universally enriched relative to their broader metagenomes. These are largely involved in (a)biotic interactions, including AMR, phage defense, virulence, biodegradation, and stress tolerance. The remainder of functions are sample-specific, suggesting that they confer localised functions relevant to their microenvironment. Together, they comprise functional profiles different from bulk metagenomes, representing niche-adaptive components of the prokaryotic pangenome.

Keywords: Bacteriology; Evolutionary biology; Molecular biology.