In laboratory studies, the transfer of plasmids carrying antimicrobial resistance (AMR) genes among bacteria occurred at significantly lower rates when zinc was present, or not at all. Halting this transfer without harming bacteria could help in mitigating AMR while preserving the gut microbiome.
The genes that facilitate antimicrobial resistance can be shared between microbes via circular pieces of genetic material known as plasmids. This sharing primarily happens in the gut. Recent research reported in Applied and Environmental Microbiology reveals that dietary zinc supplements might hinder the transmission of certain AMR plasmids.
“This discovery shows for the first time that zinc can impede plasmid transfer, and at lower concentrations, it has little effect on bacteria,” stated Melha Mellata, Ph.D., a microbiologist at Iowa State University and the study’s lead author. She emphasized its significance; eliminating gut bacteria could disturb the microbiome, leading to potential negative health consequences. “However, if we can just stop the plasmid transfer, we may be able to lessen the rise of antimicrobial resistance,” she added.
AMR infections are becoming increasingly concerning, with millions diagnosed annually and around 35,000 fatalities linked to these infections as reported by the Centers for Disease Control and Prevention. According to Mellata, when bacteria transfer AMR genes, they frequently share resistance to multiple drugs, which can result in a patient having a resistant infection even before starting antibiotic treatment. Halting plasmid transfers could be a way to curb the spread of AMR genes.
The research group in Mellata’s lab is currently exploring the relationship between gut microbiome health and overall wellness. However, they noted an interesting result in a recent study: when both a live Salmonella vaccine and probiotics were administered orally to chickens, the Enterobacteriaceae bacteria in their guts showed fewer plasmids. This finding inspired the researchers to look at other oral treatments to suppress plasmid transfer.
Logan Ott, a researcher in Mellata’s lab, spearheaded the study. He and a team of undergraduates gathered common supplements to assess their ability to inhibit plasmid transfer. They mixed these products in a testing solution and conducted numerous reactions with avian pathogenic Escherichia coli that contained a multi-drug-resistant plasmid together with a plasmid-free human E. coli isolate.
The results showed a marked decrease in plasmid transfer in bacterial strains supplemented with zinc compared to those that weren’t. Moreover, higher doses of zinc were related to lower plasmid transmission rates. While these findings were optimistic, Ott noted they were somewhat perplexing. Previous research suggested that heavy metals could enhance the conjugation process that leads to plasmid transfer. They then employed qPCR to delve deeper into the genetic impact of zinc.
“We discovered some unique mechanisms by which zinc might be causing this inhibition, whereas prior research indicated we should expect otherwise,” Ott explained. Their analysis revealed that zinc caused an overexpression of replication genes to such an extent that it likely overwhelmed and inhibited the transfer process. Furthermore, while zinc appeared to encourage the genes tied to conjugation, it also inhibited certain proteins essential for forming the bacterial structures used in the conjugation process. Consequently, overall plasmid transmission was hindered.
Looking ahead, Mellata mentioned the need to test plasmid transfer involving other AMR genes and to conduct experiments with animal models to determine if the lab findings can be replicated in vivo. Ott highlighted that our understanding of bacterial interactions and gene sharing within the gut is still limited, and future research could clarify these mechanisms.
Mellata is particularly optimistic that such an affordable and accessible supplement as zinc could play a significant role in tackling this rising threat. “Sometimes the simplest solutions come from using resources we already have on hand,” she said. “We just need to make the effort to explore them.”
