Generally used sweeteners can promote antibiotic resistance

Researchers in Australia did a study showing that commonly used non-nutritious sweeteners can promote the spread of antibiotic-resistant genes in the gut.

The study found that the sweeteners saccharin, sucralose, aspartame and acesulfame potassium promoted the horizontal transfer of genes between bacteria in both the environmental and clinical setting.

The sweeteners accelerated the exchange of antibiotic resistance genes (ARGs) through a process called conjugation. The genes are transferred from the donor to the recipient bacteria, which then may develop resistance to multiple drugs, says Zhigang Yu and colleagues from the University of Queensland in St. Lucia, Brisbane.

The team writes in the ISME Journal that the results provide insight into the spread of antibiotic resistance and indicate the potential risk associated with the presence of these sweeteners in food and beverages.

Antibiotic resistance is one of the greatest global threats

Antimicrobial resistance (AMR) is one of the world’s greatest threats to public health and biosecurity in the decades to come.

Currently, 700,000 people worldwide die each year from infections caused by antibiotic-resistant bacteria. It is estimated that 10 million people will die from such infections by 2050 if action is not taken immediately.

The appearance of ARGs that lead to resistant bacteria is generally attributed to the abuse or overuse of antibiotics.

The spread of ARGs among different types of bacteria is mainly controlled by a process called horizontal gene transfer (HGT). Conjugation is an HGT mechanism that transfers ARGs carried on mobile genetic elements such as plasmids from one bacterial cell to another. The ARGs are transmitted via a pilus or pore canal that connects the host and recipient bacteria.

Where do sweeteners come from?

Although non-nutritious sweeteners have been developed and promoted as safe food additives that enable individuals to avoid the adverse effects of sugar consumption, some commonly used sweeteners have recently been linked to health risks.

For example, in vitro studies have shown that the sweeteners saccharin (SAC), sucralose (SUC) and aspartame (ASP) can induce the formation of bladder tumors.

These sweeteners are also linked to glucose intolerance, which is believed to result from changes in the gut microbiota.

Studies have also provided evidence that SAC, SUC, and ASP, as well as acesulfame potassium (ACE-K), cause DNA damage in bacteria. The researchers say this will likely activate the DNA damage response system (SOS response).

In addition, evidence suggests that conjugative ARG transfer is related to the SOS response.

Studies have also recently shown that the use of SAC, SUC, and ASP has been linked to intestinal microbiota shifts similar to those caused by antibiotics.

“Because antibiotics can promote the spread of ARGs, we suspect that these non-nutritious sweeteners could have a similar effect,” write Yu and the team.

What did the researchers do?

Using three model conjugation systems, the team investigated whether SAC, SUC, ASP, and ACE-K promote plasmid-mediated conjugative transfer both in the environment and in the clinical setting.

The conjugation process was also visualized at the single cell level using microfluidics and confocal microscopy.

Researchers performed an analysis of whole genome RNA sequencing and measured changes in reactive oxygen species (ROS) production, the SOS response, and cell membrane permeability.

What did you find?

It was found that all four sweeteners promote plasmid-mediated conjugative transfer between the same bacteria and different phylogenetic strains.

Bacteria exposed to these compounds showed increases in ROS production, SOS response and conjugative ARG gene transfer at environmentally and clinically relevant concentrations.

Cell membrane permeability, particularly that of the donor, also played an important role in the frequency of conjugative transfer.

When the cell permeability of the donor (but not the recipient bacteria) was increased, a significant increase in conjugative transfer was observed. When the cell permeability of the recipient (but not the donor) was increased, no significant change in conjugative transfer was observed.

“It has been reported that ARG delivery has shown that donors with high expression of the conjugation machinery are associated with recipients with low susceptibility,” says Yu and colleagues. “Thus, the increased permeability of the donor can cause increased ARG transfer to the recipient and lead to an increased conjugative transfer frequency.”

What are the effects of the study?

The researchers say that studies previously showed that sewage treatment plants (sewage treatment plants) can serve as hotspots for antibiotic-resistant bacteria and ARGs due to HGT in native bacterial species.

Since the concentrations of non-nutritious sweeteners used in this study were environmentally relevant, it can be assumed that exposure to these compounds will increase the frequency of ARG transmission in sewage treatment plants, according to the team.

“It is possible that these sweeteners cause a cascading spread of ARGs in the sewage treatment plants and thus promote the development of antibiotic resistance in downstream environmental bacteria,” write Yu and colleagues.

“Given the significant use of these sweeteners in the food industry (over 117,000 tonnes consumed worldwide each year), our results are a wake-up call to begin assessing the potential antibiotic-like roles that non-nutritious sweeteners have,” it concludes Team.

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