Microbial regulation of natural antibiotic resistance: Understanding the protist-bacteria interactions for evolution of soil resistome.

The emergence, evolution and spread of antibiotic resistance genes (ARGs) in the environment represent a global threat to human health. Our knowledge of antibiotic resistance in human-impacted ecosystems is rapidly growing with antibiotic use, organic fertilization and wastewater irrigation identified as key selection pressures. However, the importance of biological interactions, especially predation and competition, as a potential driver of antibiotic resistance in the natural environment with limited anthropogenic disturbance remains largely overlooked. Stress-affected bacteria develop resistance to maximize competition and survival, and similarly bacteria may develop resistance to fight stress under the predation pressure of protists, an essential component of the soil microbiome. In this article, we summarized the major findings for the prevalence of natural ARGs on our planet and discussed the potential selection pressures driving the evolution and development of antibiotic resistance in natural settings. This is the first article that reviewed the potential links between protists and the antibiotic resistance of bacteria, and highlighted the importance of predation by protists as a crucial selection pressure of antibiotic resistance in the absence of anthropogenic disturbance. We conclude that an improved ecological understanding of the protists-bacteria interactions and other biological relationships would greatly expand our ability to predict and mitigate the environmental antibiotic resistance under the context of global change.