Biological Mitigation of Antibiotic Resistance Gene Dissemination by Antioxidant-Producing Microorganisms in Activated Sludge Systems

Abstract

Antibiotic resistance is the principal mechanism of an evergrowing bacterial threat. Antibiotic residues in the environment are a major contributor to the spread of antibiotic resistance genes (ARGs). Subinhibitory concentrations of antibiotics cause bacteria to produce reactive oxygen species (ROS), which can lead to mutagenesis and horizontal gene transfer (HGT) of ARGs; however, little is known about the mitigation of ARG dissemination through ROS removal by antioxidants. In this study, we examine how antioxidant-producing microorganisms inoculated in replicate activated sludge systems can biologically mitigate the dissemination of ARGs. Through quantitative polymerase chain reaction (qPCR), we showed that antioxidant-producing microorganisms could decrease the persistence of the RP4 plasmid and alleviate enrichment of ARGs (sul1) and class 1 integrons (intl1). Metagenomic sequencing identified the most diverse resistome and the most mutated Escherichia coli ARGs in the reactor that contained antibiotics but no antioxidant-producing microorganisms, suggesting that antioxidant-producing microorganisms mitigated ARG enrichment and mutation. Host classification revealed that antioxidant-producing microorganisms decreased the diversity of ARG hosts by shaping the microbial community through competition and functional pathway changes. Conjugative experiments demonstrated that conjugative transfer of ARGs could be mitigated by coculture with antioxidant-producing microorganisms. Overall, this is a novel study that shows how ARG enrichment and HGT can be mitigated through bioaugmentation with antioxidant-producing microorganisms.

Antimicrobial and the Resistances in the Environment: Ecological and Health Risks, Influencing Factors, and Mitigation Strategies

“…Therefore, the mitigation and treatment of antimicrobial resistance and antimicrobial contamination from the perspective of removing ARGs and antimicrobials may be a more effective strategy. Constructed wetlands (CW), advanced oxidation processes (AOP), membrane processes, and microbial fuel cells (MFC) have been reported as promising elimination methods for pollutants [ 122 , 160 , 161 , 162 , 163 ]. In the following, we summarize the existing, relatively efficient and promising antimicrobial and ARGs elimination methods.…”

“…In polluted water sources, ARGs abundance showed a relatively strong correlation with the concentration of heavy metals [ 121 ]. Reactive oxygen species are thought to be the inducement of ARGs transfer, but not the only one [ 122 ]. The presence of heavy metal ions can cause oxidative stress in bacteria, and then increase intracellular reactive oxygen species levels, which may serve as a potential mechanism of heavy metals promoting the formation of ARB [ 123 ].…”

Synthetic Nuclease-Producing Microbiome Achieves Efficient Removal of Extracellular Antibiotic Resistance Genes from Wastewater Effluent

“…In our previous study, we demonstrated that the nucleaseproducing Deinococcus could mitigate transformation of extracellular ARGs to Enterococcus faecalis by degrading eDNA. 18,19 Therefore, this study mainly demonstrates whether these nuclease-producing bacteria can reduce the risk of ARG dissemination in mixed bacteria sewage systems. In this study, a microbiome capable of degrading eDNA was constructed and operated by using Deinococcus radiodurans as the base microorganism.…”

A Carotenoid- and Nuclease-Producing Bacterium Can Mitigate Enterococcus faecalis Transformation by Antibiotic Resistance Genes

“…For example, bacteria belonging to the Deinococcus , Myxococcus , Streptomyces , Flectobacillus , Exiguobacterium , and Sphingomonas genera are known to defend against oxidative stress by producing reducing substances such as carotenoids, exopolysaccharides, and small-molecule antioxidants that efficiently scavenge ROS . We previously showed that antioxidant-producing bacteria can scavenge excess ROS (induced by antibiotics) in activated sludge, although the underlying mechanisms and genetic basis were not discerned. In addition, many bacteria are separately capable of synthesizing extracellular nucleases that degrade eDNA .…”