Antibiotic resistance selection and deselection in municipal wastewater from 47 countries – Nature

Report on Antibiotic Resistance Selection in Global Municipal Wastewater

Executive Summary

Antimicrobial Resistance (AMR) poses a significant threat to global public health, undermining progress towards Sustainable Development Goal 3 (Good Health and Well-being). Municipal wastewater is a critical environmental nexus where resistant bacteria and selective agents converge, directly impacting SDG 6 (Clean Water and Sanitation). This report details an experimental investigation into the potential of untreated municipal wastewater from 47 countries to select for antibiotic resistance. Using a functional selection assay, the study found that while sterile-filtered wastewater from 14 countries significantly selected for resistance to at least one antibiotic class, the majority of samples selected against resistance. A comprehensive chemical analysis identified 22 antibiotics and 13 antibacterial biocides, but their measured concentrations correlated weakly with observed selection, suggesting complex mixture effects or selection by unmeasured compounds. The prevalent deselection of resistance indicates that many resistant strains exhibit impaired fitness in wastewater environments with limited antibiotic pressure. These findings underscore the complex role of wastewater in AMR dynamics and highlight the critical importance of robust sanitation infrastructure in achieving global health and environmental sustainability goals.

1.0 Introduction: A Global Health and Environmental Challenge

1.1 Antibiotic Resistance and the Sustainable Development Goals

The rise of antibiotic resistance is a global crisis that jeopardizes modern medicine, food security, and public health, directly challenging the achievement of SDG 3. The external environment, particularly aquatic systems, is increasingly recognized as a crucial arena for the evolution and transmission of resistance. This environmental dimension of AMR links public health outcomes to the management of water resources and sanitation systems, creating a strong interdependency with SDG 6, SDG 11 (Sustainable Cities and Communities), and SDG 14 (Life Below Water).

1.2 Wastewater as a Critical Nexus for AMR and SDG 6

Municipal wastewater treatment plants (WWTPs) are focal points where bacteria from human and environmental sources mix with residual antibiotics and other chemical agents. This creates a potential hotspot for the selection of antibiotic resistance genes (ARGs) and their horizontal transfer. Effective management of municipal wastewater is therefore a cornerstone of both urban sustainability (SDG 11) and the protection of public and environmental health. This study addresses a critical knowledge gap by empirically assessing the selective pressure exerted by municipal wastewater on a global scale, providing data essential for risk assessment and the development of strategies aligned with the One Health approach and multiple SDGs.

2.0 Methodology: A Global Surveillance Approach

This investigation was conducted as part of the Global Sewage Surveillance Project, a collaborative effort exemplifying SDG 17 (Partnerships for the Goals).

2.1 Sample Collection and Analysis

• Untreated municipal wastewater samples were collected from 49 cities across 47 countries.
• Samples were sterile-filtered to isolate the chemical components responsible for selective pressure.
• Concentrations of 22 antibiotics and 20 antibacterial biocides were quantified using online solid phase extraction liquid chromatography-tandem mass spectrometry (OSPE-LC-MS/MS).

2.2 Assessing Selection Potential

1. A synthetic community of 340 diverse Escherichia coli strains was exposed to the sterile-filtered wastewater samples for 72 hours.
2. The change in the proportion of bacteria resistant to five major antibiotic classes was measured and compared to a baseline to determine the selection potential.
3. Findings were validated using a subset of samples tested with natural wastewater microbial communities to ensure the results were not an artifact of the synthetic community.

3.0 Key Findings: Selection and Deselection Dynamics

3.1 Global Patterns of Antibiotic Resistance Selection

The study revealed a complex pattern of both selection and deselection for antibiotic resistance across the global samples.

• Positive Selection: Wastewater from 14 countries exerted significant positive selection for resistance to at least one antibiotic. The sample from Nigeria demonstrated selection for all five tested antibiotic classes. This finding confirms that certain municipal wastewater environments can actively promote the proliferation of resistant bacteria, posing a direct risk to public health (SDG 3).
• Deselection (Selection Against Resistance): A majority of samples (40 out of 49) significantly selected against at least one type of resistance. This deselection was the dominant trend, suggesting that in the absence of strong antibiotic pressure, resistant bacteria are often at a competitive disadvantage. This ecological dynamic could be leveraged in strategies to mitigate AMR spread.

3.2 Chemical Drivers of Resistance: Antibiotics and Biocides

The chemical analysis provided context for the observed selection patterns and their relevance to responsible consumption and production (SDG 12).

• Antibiotics: Of the 22 antibiotics analyzed, 21 were detected. However, their concentrations were generally far below levels predicted to select for resistance in E. coli. Folate pathway antagonists and macrolides were exceptions, often exceeding predicted no-effect concentrations (PNECs) for other bacterial species, indicating a potential risk for resistance selection in the broader microbial community.
• Antibacterial Biocides: The analysis confirmed the presence of 13 different organic antibacterial biocides, highlighting the chemical complexity of municipal wastewater. However, due to a lack of established co-selective concentration data, their contribution to antibiotic resistance selection remains unclear.

3.3 Correlation Analysis and Unidentified Drivers

Regression analysis revealed only weak correlations between the concentrations of measured chemicals and the observed selection for resistance. This suggests that the selection pressure in municipal wastewater is not driven by single compounds but is likely the result of complex mixture effects or the presence of unmeasured selective agents. This complexity underscores the challenge of managing chemical pollution to protect water quality and public health as mandated by SDG 6.

4.0 Discussion: Implications for Sustainable Development

4.1 The Ecological Balance and Wastewater Management

The frequent observation of deselection is a critical finding, suggesting that well-managed wastewater systems with low concentrations of selective agents may naturally reduce the prevalence of resistant bacteria. This highlights an opportunity to design and operate WWTPs not only for pathogen removal but also to create conditions that favor susceptible bacteria, thereby contributing to both SDG 3 and SDG 6. Conversely, the evidence of positive selection in nearly 30% of locations confirms that inadequate wastewater management can transform sanitation systems into incubators for AMR.

4.2 Addressing SDG 3 and SDG 6 through Integrated Strategies

The study demonstrates that monitoring and managing the chemical composition of wastewater is essential for mitigating AMR. The presence of antibiotics and biocides, even at low levels, reflects patterns of consumption and disposal within communities (SDG 12). To protect public health (SDG 3), it is imperative to improve sanitation infrastructure (SDG 6) and implement policies that reduce the discharge of selective agents into sewer systems. This requires an integrated One Health approach that connects clinical practice, community behavior, and environmental engineering.

5.0 Conclusion and Recommendations

This global study provides empirical evidence that municipal wastewater can act as an environment for both the selection and deselection of antibiotic resistance. While the selection for resistance in certain wastewaters presents a clear threat to global health, the more common phenomenon of deselection suggests that resistant bacteria face a fitness cost in many aquatic environments.

To advance the Sustainable Development Goals, the following actions are recommended:

1. Enhance Wastewater Surveillance: Implement routine monitoring of selective agents and resistance levels in municipal wastewater as a tool for public health surveillance, directly supporting SDG 3 and SDG 6.
2. Invest in Sanitation Infrastructure: Prioritize investment in advanced wastewater treatment technologies, particularly in regions showing high selective potential, to reduce the environmental burden of AMR.
3. Promote Responsible Consumption: Develop policies and public awareness campaigns to reduce the unnecessary use and improper disposal of antibiotics and biocides, aligning with SDG 12.
4. Foster International Collaboration: Continue and expand global surveillance partnerships, such as the one that enabled this study, to share data and best practices for AMR mitigation, reinforcing SDG 17.

Analysis of Sustainable Development Goals (SDGs) in the Article

1. Which SDGs are addressed or connected to the issues highlighted in the article?

The article on antibiotic resistance in municipal wastewater connects to several Sustainable Development Goals (SDGs) due to its focus on public health, water quality, environmental pollution, and international scientific collaboration. The following SDGs are relevant:

• SDG 3: Good Health and Well-being: The core issue of the article is antibiotic resistance, which is described as a “pressing challenge to public health.” The evolution and transmission of resistant pathogens directly threaten the effective treatment of bacterial infections, undermining global health security.
• SDG 6: Clean Water and Sanitation: The study centers on municipal wastewater as a medium for the evolution and spread of antibiotic resistance. It investigates the quality of untreated wastewater from 47 countries, directly addressing the issue of water pollution from chemical contaminants like antibiotics and biocides.
• SDG 11: Sustainable Cities and Communities: The research focuses on “municipal wastewater,” which is a critical component of urban waste management. The presence and concentration of pollutants in sewage from 49 cities highlight the environmental impact of urban centers and the need for effective wastewater management to create sustainable communities.
• SDG 12: Responsible Consumption and Production: The presence of antibiotics and biocides in wastewater is a direct result of their consumption and subsequent disposal into the environment. The article implicitly addresses the need for environmentally sound management of these chemicals to reduce their release into water systems.
• SDG 14: Life Below Water: Although not directly studying marine ecosystems, the article’s focus on wastewater pollution is highly relevant. Wastewater treatment plants are a primary source of land-based pollution, and the discharge of untreated or poorly treated wastewater containing antibiotics and resistant bacteria can severely impact aquatic ecosystems.
• SDG 17: Partnerships for the Goals: The study itself is an example of this SDG in action. It is part of the “Global Sewage Surveillance Project,” a large-scale international collaboration involving the collection and analysis of wastewater samples from 47 countries to address the global challenge of antimicrobial resistance.

2. What specific targets under those SDGs can be identified based on the article’s content?

Based on the issues discussed, several specific SDG targets can be identified:

1. Under SDG 3 (Good Health and Well-being):
   • Target 3.3: “By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases.” The article’s focus on antibiotic resistance is crucial for this target, as resistance undermines the ability to treat and control communicable bacterial diseases.
   • Target 3.d: “Strengthen the capacity of all countries… for early warning, risk reduction and management of national and global health risks.” The research, which uses wastewater surveillance to monitor antibiotic resistance on a global scale, directly contributes to developing systems for early warning and risk management of the global health threat of antimicrobial resistance (AMR).
2. Under SDG 6 (Clean Water and Sanitation):
   • Target 6.3: “By 2030, improve water quality by reducing pollution, eliminating dumping and minimizing release of hazardous chemicals and materials, halving the proportion of untreated wastewater…” The article directly addresses this target by investigating pollution in untreated municipal wastewater. It quantifies the “release of hazardous chemicals” (22 antibiotics and 20 antibacterial biocides) into water systems.
3. Under SDG 11 (Sustainable Cities and Communities):
   • Target 11.6: “By 2030, reduce the adverse per capita environmental impact of cities, including by paying special attention to… municipal and other waste management.” The study’s analysis of municipal wastewater from dozens of cities provides data on the environmental impact of urban waste, highlighting the need for improved management to mitigate pollution.
4. Under SDG 12 (Responsible Consumption and Production):
   • Target 12.4: “By 2020, achieve the environmentally sound management of chemicals and all wastes throughout their life cycle… and significantly reduce their release to air, water and soil…” The article’s detailed analysis of antibiotic and biocide concentrations in wastewater directly relates to monitoring the release of these chemicals into water, a key step in their sound management.
5. Under SDG 14 (Life Below Water):
   • Target 14.1: “By 2025, prevent and significantly reduce marine pollution of all kinds, in particular from land-based activities…” Municipal wastewater is a primary land-based source of pollution. The study characterizes contaminants that can enter and harm aquatic environments, thus providing crucial information for achieving this target.
6. Under SDG 17 (Partnerships for the Goals):
   • Target 17.6: “Enhance North-South, South-South and triangular regional and international cooperation on and access to science, technology and innovation…” The study is a product of the “Global Sewage Surveillance Project,” which coordinated sampling in 47 countries, exemplifying international scientific cooperation to tackle a shared global problem.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

Yes, the article mentions and uses several quantitative measures that can serve as indicators for tracking progress towards the identified targets:

• For Target 6.3 (Improve water quality):
  • Concentrations of specific pollutants in wastewater: The article provides a “comprehensive characterization of antibiotics and antibacterial biocides in the wastewaters.” It measures the concentrations of 22 different antibiotics (e.g., ciprofloxacin, sulfamethoxazole) and 20 biocides. These measurements serve as direct indicators of chemical pollution in water, aligning with Indicator 6.3.2 (Proportion of bodies of water with good ambient water quality).
  • Comparison to Predicted No-Effect Concentrations (PNECs): The study compares measured antibiotic concentrations to PNECs, which are “proposed limits for environmental regulation.” This ratio (Measured Concentration/PNEC) is a powerful indicator for assessing the environmental risk of pollution and the effectiveness of management strategies.
• For Target 3.d (Manage global health risks):
  • Selection potential for antibiotic resistance: The primary experimental assay in the study measures the “selection potential” of wastewater, defined as “the change in the proportion of bacteria resistant (%resistance)” after exposure. This functional measure is a direct indicator of the environmental pressure driving the evolution of AMR, a key global health risk.
  • Abundance of Antibiotic Resistance Genes (ARGs): The article references and uses data on the “relative ARG and biocidal resistance gene (BRG) abundances” from metagenomic analyses of the same wastewater samples. The abundance of ARGs in municipal sewage is an established indicator for AMR surveillance at a population level.
• For Target 12.4 (Sound management of chemicals):
  • Quantification of chemical release: The measurement of antibiotic and biocide concentrations in wastewater from 47 countries provides a baseline indicator of the scale of chemical release into the environment from municipal sources, which is essential for evaluating the effectiveness of policies aimed at reducing chemical waste.

4. Summary Table of SDGs, Targets, and Indicators

Source: nature.com