Microbial regulation of antibiotic resistance:Effects of protists on bacterial antibiotic resistance
Since Alexander Fleming's discovery of penicillin in 1928,numerous antibiotics have been discovered and produced industrially.Approximately,30％to 90％of antibiotics cannot be absorbed by humans and animals and,are released into the environment in different forms.As a result,antibiotics are much more concentrated in human-affected environments than in natural environments,forming a pervasive selection pressure and accelerating the evolution and emergence of antibiotic resistance genes(ARGs).With ongoing research,we are gradually gaining more insights into how human activities impact ARGs.However,in natural environments with little anthropogenic disturbance,microbial interactions are the main drivers of antibiotic resistance,which have been largely overlooked.Protists are central to a wide array of food web processes and biogeochemical cycles,and deserve more attention.It is well documented that protists prey on bacteria,the main carriers of ARGs.Thus,protists can indirectly affect resistome by changing bacterial community structure through predation.Likewise,antibiotics are secreted by bacteria as a means of avoiding predation by protozoa,increasing the selective pressure on the environment.Therefore,understanding the relationship between protists and bacterial antibiotic resistance will help us improve the ability to predict and manage microbes to better guide agricultural production,reduce antibiotic overuse and prevent or mitigate the emergence of new antibiotic resistance.This paper first introduces the origin,evolution and spread of antibiotic resistance,and then summarizes that the main factors driving its evolution vary from the pre-antibiotic era to the antibiotic era.In the second section,this paper reviews that autotrophic protists may contribute to the reduction of antibiotic resistance:(1)By bioadsorption,bioaccumulation,and biodegradation,autotrophic protists can remove antibiotics from the environment,reducing selection pressure and slowing the speed of evolution;(2)autotrophic protists can secrete some secondary metabolites,including alternatives to antibiotics,quorum sensing inhibitors,and efflux pump inhibitors,all of which contribute to reducing antibiotic resistance.Besides,phagocytic protists also play an important role.In addition to serving as the hotspot for horizontal gene transfer(HGT),they also stimulate bacteria to secrete antibiotics through predation and increase the frequency of HGT between different bacteria.Since individual level studies do not represent the actual situation of communities in natural environments,research on the community level is required.Therefore,the third section is focused on the community level.Protists display a myriad of sizes,morphologies and nutritional modes,making it difficult to study them with the traditional method.The ultra-deep high-throughput sequencing combined with statistical approaches provides new insights into the conundrum of how protists regulate bacterial antibiotic resistance at the community level.It is noteworthy that studies based on sequencing data also have their limitations.First of all,data requirements are high,that is,a large number of samples and key environmental variables need to be covered.Secondly,the results are data-driven and need to be verified by other experiments.The last section discusses perspectives regarding the role of protists in preventing and controlling the risk of bacterial antibiotic resistance:(1)Screening secondary metabolites from autotrophic protists,searching for substances that can reduce antibiotic resistance,and realizing industrial production;(2)protists should be considered as one of the indicators of environmental monitoring,especially in hospitals,preventing intracellular bacteria from becoming super-resistant bacteria via HGT;(3)it is necessary to develop novel disinfection techniques to kill antibiotic resistant bacteria protected by protist cysts;and(4)the regulating mechanisms between protists and bacterial antibiotic resistance should be explored at the community level.
antibiotic resistance genesprotistindividual levelcommunity levelmicrobial interactionhorizontal gene transfer
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