Nonnutritive sweeteners can promote the dissemination of antibiotic resistance through conjugative gene transfer

Abstract

Antimicrobial resistance (AMR) poses a worldwide threat to human health and biosecurity. The spread of antibiotic resistance genes (ARGs) via conjugative plasmid transfer is a major contributor to the evolution of this resistance. Although permitted as safe food additives, compounds such as saccharine, sucralose, aspartame, and acesulfame potassium that are commonly used as nonnutritive sweeteners have recently been associated with shifts in the gut microbiota similar to those caused by antibiotics. As antibiotics can promote the spread of antibiotic resistance genes (ARGs), we hypothesize that these nonnutritive sweeteners could have a similar effect. Here, we demonstrate for the first time that saccharine, sucralose, aspartame, and acesulfame potassium could promote plasmid-mediated conjugative transfer in three established conjugation models between the same and different phylogenetic strains. The real-time dynamic conjugation process was visualized at the single-cell level. Bacteria exposed to the tested compounds exhibited increased reactive oxygen species (ROS) production, the SOS response, and gene transfer. In addition, cell membrane permeability increased in both parental bacteria under exposure to the tested compounds. The expression of genes involved in ROS detoxification, the SOS response, and cell membrane permeability was significantly upregulated under sweetener treatment. In conclusion, exposure to nonnutritive sweeteners enhances conjugation in bacteria. Our findings provide insight into AMR spread and indicate the potential risk associated with the presence of nonnutritive sweeteners.

Artificial Sweeteners Negatively Regulate Pathogenic Characteristics of Two Model Gut Bacteria, E. coli and E. faecalis

“…Indeed, whilst studies indicate the potential for olfactory responses in Bacillus licheniformis , there is no literature indicating the presence of a sweet taste receptor or sensor in bacteria which could respond to artificial sweeteners [ 50 ]. Instead, there is evidence that sweeteners can cause DNA damage in bacteria, elevate bacterial mutation rate in a dose-dependent manner or ROS production and detoxification, and increase cell membrane permeability [ 51 , 52 , 53 , 54 ]. ROS can modulate the quorum sensing ability of bacteria to sense and respond to their environment [ 55 , 56 ] therefore sweeteners may impact pathogenicity of model gut bacteria in the present study through a ROS-dependent pathway.…”

“…Globally, sweeteners (acesulfame, saccharin, and sucralose) have been detected in wastewater, surface water, groundwater, and drinking water systems [ 61 , 62 , 63 ]. More worryingly, artificial sweeteners have been linked to increased horizontal transfer of antimicrobial resistance genes in environmental and clinical settings [ 52 , 54 ]. In addition, increased biofilm formation is believed to cause medical device-associated infections and is closely linked to the antibiotic-resistant bacteria, which is now a widespread public health threat [ 64 , 65 , 66 , 67 ].…”

Artificial sweeteners stimulate horizontal transfer of extracellular antibiotic resistance genes through natural transformation

“…Accordingly, we hypothesized that these widely-used food additives [13][14][15] might also contribute to the dissemination of antibiotic resistance among bacteria. Our recent study has demonstrated that the widely-used artificial sweeteners can promote horizontal transfer of ARGs via conjugation [16]. These sweeteners promoted pili formation and increased expression of conjugative transfer-related genes located on the plasmid.…”

Combined impact of TiO2 nanoparticles and antibiotics on the activity and bacterial community of partial nitrification system

“…In the Nano&Tet group and the Nano&Ery group, PI uptake was much higher than that in the Tet group and the Ery group, suggesting that the combined impacts significantly decreased the antibiotic resistance of the systems [ 31 , 32 ]. Bacteria can reduce intracellular availability of antibiotics by inhibiting or replacing outer membrane porins and overexpressing efflux pumps.…”

“…After washed twice with 0.85% (w/v) NaCl solution, the bacterial suspension was diluted to a cell density with an optical density at 600 nm (OD 600 ) of 0.10±0.02 [ 30 ]. One mL of bacterial suspension was stained with 10 μl of propidium iodide (PI) (1 mg/ml, OMEGA, USA) and incubated in the dark for 8 min before measurement [ 31 , 32 ]. The cell permeability was tested by flow cytometry analysis (FCM, BD FACSCalibur, USA) and PI fluorescent signal was excited by 488 nm.…”