Antimicrobial Resistance in Exploited Estuaries: Some Overlooked Environmental Contaminants and Microbial Niches Might Act as Drivers

Antibiotic resistance is one of the most serious threats to human health and food safety, carrying a dramatic cost to society both financially and in terms of human suffering. The Organisation for Economic Co-operation and Development (OECD) has estimated that over the next 30 years, infections involving resistant bacteria could cost the lives of 2.4 million people in Europe, North America, and Australia, at an estimated cost of 3.5 billion dollars a year (OECD, 2018). Because antibiotics are natural or synthetic chemical compounds that inhibit the development or cause the death of microorganisms, they are widely used (and sometimes overused) in human healthcare for the treatment of bacterial infections; in animal care they are employed to prevent disease and promote livestock growth. Antibiotics utilized in animal farm production constitute the greatest use worldwide; it has been estimated that more than 130 000 t were used for this purpose in 2013, an amount that could exceed 200 000 t in 2030 (Boeckel et al., 2017). Even though the available data are incomplete, this number would be significantly increased with the inclusion of human therapeutic use. These antibiotics reach the environment at different stages of an organism's life cycle and through different routes (manufacturing efflux, excretion after consumption and metabolization, inappropriate disposal or recycling, etc.). This continuous release leads to the detection of antibiotics in surface waters and estuarine areas, where they have been measured at concentrations ranging from 10 ng/L to μg/L, depending on the location; traces have also been detected in drinking water (Zheng et al., 2021). Such contamination is a driving factor in the development of bacterial resistance. Even if the acquisition of resistance is a natural adaptive mechanism, increased acquisition can be seen in response to an increase in antibiotic use, while at the same time the efficiency of newly developed antibiotics rapidly decreases. Bacteria may become resistant to antibiotics via mutations, leading to the establishment of mechanisms that inactivate the antibiotic, increase the efflux of the molecule outside the bacterial cell, or modify the target protein. The second resistance strategy consists of the acquisition of genetic material through horizontal gene transfer (HGT); if the antibiotic resistance gene (ARG) is transferred, it confers a new function (resistance) on the target bacteria. Thus antibiotics are a gold standard for exerting high selection pressure on bacteria and triggering the occurrence of specific ARGs. However, environmental pollutants such as metals, polycyclic aromatic hydrocarbons, or pesticides have also been shown to exert selection pressure by causing cross-resistance to antibiotics or inducing HGT. In most cases, these xenobiotics, which originate from industrial and agricultural activities, are more prevalent than antibiotics in ecosystems and are able to activate genes encoding for efflux pumps, which in turn cause a decrease in the active concentration of compounds (including antibiotics) inside the bacterial cell (Blanco et al., 2016). Thus we urgently need to decipher the role of nonantibiotic contaminants in the induction of ubiquitous resistance to molecules that the bacteria might never have been exposed to. In the environment, aquatic ecosystems are thought to constitute major reservoirs of resistance genes and to favor their spread into other ecosystems, including estuarine areas. In particular, it is now recognized that wastewater treatment plants (WWTPs) constitute hotspots for environmental diffusion of pollutants and antibiotic-resistant bacteria (ARBs), which may be only partially eliminated during treatment, depending on the facility's level of technology. This leads to discharge into aquatic ecosystems through effluents and also into terrestrial ecosystems following the spread of sewage sludge or manure from farm animals. Thus resistant bacteria are detected downstream of WWTPs worldwide (Grenni, 2022). Runoff and transport via rivers and streams allow these contaminants to reach estuaries. An understanding of the development, retention, and diffusion of antimicrobial resistance (AMR) in estuaries is critical because they act as natural filtering points for chemical and biological pollutants at the boundary between terrestrial/freshwater and marine ecosystems. In addition, estuarine areas are highly productive systems; they supply resources for natural living populations and also for human consumption. Liguori et al. (2022) have laid out a framework for monitoring water environments and standardizing methods. However, most of the studies on the occurrence of ARGs consist of gene quantification in biota such as water columns or sediment while the role of other microbiological compartments with a high potential to act as incubators of AMR is often not considered. In particular, the commensal microbiotas of organisms that encourage auspicious conditions such as high microbial diversity and density can facilitate AMR and HGT, as observed in the human intestine after medical treatment. Thus particular attention should be paid to such microbiological niches, which are poorly investigated and may contribute to environmental dissemination of ARGs through release of feces or trophic transfer between organisms. In addition, it has been suggested that microplastics also contribute to the antibiotic resistance crisis, in a different manner. Microplastics are found downstream of WWTPs, emptying into the oceans and threatening the ecological functioning of both stream and estuarine ecosystems. They may be potential carriers of AMR because they provide new ecological niches for the development of ARG-containing biofilms, facilitating the spread of resistance into an environment (Bank et al., 2020). Thus, concomitantly with the general study of ARGs, monitoring the dynamics of microplastics could help us to better understand and characterize the spread of ARGs along the land–sea continuum and to define the risk associated with microplastic-transported ARGs in aquatic environments. These microplastics might contribute to human exposure because they are accumulated by multiple organisms, including living resources consumed by humans. In particular, organisms such as oysters, which are often eaten raw, are species of interest for the monitoring of AMR because their contamination by ARBs involves food safety and human health, exposing humans to unaltered AMR-containing microbiomes. Ingestion of contaminated food may lead to colonization of the human digestive tract by resistant bacteria. Because HGT may occur between phylogenetically distant prokaryote cells from different niches (von Wintersdorff et al., 2016), resistance may therefore be acquired by bacteria from the human gut microbiota. If the bacterium receiving the gene is pathogenic, then the related infection could be untreatable. In this context, we urgently need to improve our understanding of how aquatic and estuarine environments are involved in this crisis of antibiotic resistance, to help stakeholders improve environmental management and mitigate the spread of AMR and to prevent or reduce transmission to human populations; otherwise the action plans to counter the expansion of such resistance may not achieve their objectives. The author declares no conflict of interest. Lauris Evariste: Conceptualization; Writing—original draft.