Antibiotic resistance in water environment: Frontiers of fundamental research, risk assessment and control strategies

Abstract

Antibiotic resistance has been considered as a major health security challenge of the 21st century in the 2013 G8 Science Minsters Statement. UN Environment ranked "Antimicrobial Resistance: Investigating the Environmental Dimension" as No.1 emerging issue among the six emerging issues of environmental concern in 2017. It should be pointed out that antibiotic resistance is not just a regional or national phenomenon but also a global problem, indicated by the famously typical cases of the rapid dissemination of Klebsiella pneumonia carbapenemase-positive bacteria and New Delhi metallo- β-lactamase-positive bacteria in Asia, Europe and North America. Animal waste, antibiotic production wastewater, hospital wastewater, sewage, sludge, soil, sediment, surface water and even air have been considered as important reservoirs for antibiotic resistance genes (ARGs) because abundant ARGs have been frequently detected in these environments. Among the different environment types, the water environment is a key node for the dissemination of antibiotic resistance. A large number of previous studies mainly focused on the abundance and diversity of ARGs in the water environments. However, the systematic and in-depth studies on the source, spread and fate of ARGs in the water environment are still limited. The basic framework and sophisticated models for risk assessment are still lacking for environments even possessing data of antibiotic concentration and exposure levels of ARGs. In addition, there is also no strategic thinking in the formulation and implementation of antibiotic resistance control strategies. Considering the above issues, this review will focus on the frontiers of fundamental research, risk assessment, and control strategies of antibiotic resistance in water environment and other environments, including: (1) The establishment of standardized detection approach and public database for antibiotics, i.e., the major selection pressure of antibiotic resistance; (2) the migration, transformation and bioavailability of antibiotics; (3) the transfer and dissemination of ARGs in the wastewater treatment plants; (4) exploring the standardized methods for investigating exposure levels of ARGs: metagenomic approach & highthroughput qPCR approach; (5) the key mobile genetic elements responsible for horizontal gene transfer and environmental transmission of ARGs; (6) deep mining and machine learning of ARGs using metagenomic/genomic big data. Several case studies were selected respectively to demonstrate current research status of the above six frontiers of fundamental research, risk assessment, and control strategies of antibiotic resistance. For the risk assessment, two types of risks including the risk of antibiotic treatment failure and the risk of ARGs dissemination in the environment should be distinguished. The prevention and control strategy of antibiotic resistance involves multi-disciplinary linkage and combination together, which requires the joint efforts of clinical medicine, ecology, agriculture, pharmacy, environmental science and engineering, as well as the cooperation of education, etc. Currently, following the integrative strategy of One Health, we should give the first priority to the investment on prevention and control measures at the key emission sources and other nodes to effectively reduce and ultimately stop the emissions of antibiotics and ARGs. The key emission sources mainly include antibiotic manufacturing factory, livestock farm, aquaculture farms, slaughter house, hospital and municipal wastewater treatment plants etc.