The effects of environmental metals on the spread of antimicrobial resistance genes in the stickleback skin microbiome

Antimicrobial resistance (AMR) is a major threat to humans, animals, and our environment. Although this is often associated with the misuse and overuse of antibiotics in human and livestock-dominated environments, its wider environmental occurrence is poorly understood. Emerging evidence suggests that AMR genes (ARGs) are frequently identified in commensal organisms, such as members of host-associated and environmental microbiomes. This poses a major risk as commensal-resistant organisms might serve as a reservoir of resistance genes that can be horizontally transferred to pathogens or cause opportunistic infections in the future.

To effectively combat AMR, we need to understand how environmental variation (e.g., pH and temperature) encourages the spread of ARGs between bacteria (i.e., horizontal gene transfer (HGT). It has been shown that resistance to metals (e.g., copper, zinc, lead, etc.) and AMR are often co-selected in bacterial genomes and directly correlate with environmental metal levels (Pal C et al. 2017 Adv Micro Physio).

The three-spined stickleback is a well-studied model organism native to fresh and oceanic northern waters. While a variety of environmental factors have been associated with the composition of their gut microbiome (Rennison et al. 2019 Proc Royal Soc B), the skin microbiome remains under-explored. The skin of fish, a mucus membrane in direct contact with the environment, is an important mechanism in infection prevention and ideal for microbiome study (Reverter et al., 2018 Fish Sahul).

This project investigates whether environmental variation in metal concentrations on the island of North Uist, Scotland, leads to increased presence, abundance, and spread (via HGT) of ARGs in stickleback skin microbiomes. To address the objective of the project, we will:
a. Sequence the skin microbiome (and the surrounding water to determine background bacterial contamination (Krotman et al. 2020 Microbiome)) of stickleback populations, and account for genotype/environmental differences
b. Culture the microbiome and profile AMR bacteria
c. Also, in the Nottingham aquariums, colonize gnotobiotic (i.e., germ-free) fish with a skin microbiome from low- vs. high-metal environments will be studied, and longitudinally sample the skin microbiome to identify new HGT events.
The study will provide valuable insight into how environmental variations can provide favourable conditions for the transfer of ARGs and offer effective strategies to combat antibiotic resistance.