Periodic Reporting for period 1 - PHASTER (Bacteriophages as vehicles for antimicrobial resistance determinants: Do they represent an environmental risk?)
Periodo di rendicontazione: 2023-05-01 al 2025-04-30
For PHASTER project, we have identified that microbial communities are dynamic ecosystems in constant flux, continuously shaped by environmental pressures and human activities. However, significant gaps remain in our overall understanding, particularly in relation to the spread of antimicrobial resistance (AMR) within microbial populations due to the presence of phages (viruses that infect bacteria). This process may be significantly influenced by low concentrations of antibiotics, which are commonly found in natural environments due to agricultural runoff, wastewater discharge, and other anthropogenic sources.
This project seeks to uncover how phages contribute to the horizontal gene transfer of antibiotic resistance genes (ARGs) under these real-world conditions. The results are expected to provide key insights into the mechanisms by which resistance spreads silently in the environment, often going unnoticed until it reaches a critical threshold with direct implications for public health. This knowledge is especially relevant in the current political and strategic context, where global agencies such as the World Health Organization (WHO) and the European Commission have prioritized the fight against AMR as one of the major challenges of the 21st century.
This project seeks to uncover how phages contribute to the horizontal gene transfer of antibiotic resistance genes (ARGs) under these real-world conditions. The results are expected to provide key insights into the mechanisms by which resistance spreads silently in the environment, often going unnoticed until it reaches a critical threshold with direct implications for public health. This knowledge is especially relevant in the current political and strategic context, where global agencies such as the World Health Organization (WHO) and the European Commission have prioritized the fight against AMR as one of the major challenges of the 21st century.
WP1 – Occurrence and prevalence of phages harbouring ARGs in environmental settings.
One of the main hypotheses in PHASTER is that human perturbations can increase the prevalence of phages harbouring ARGs in the environment. Recent studies have suggested that selection of antibiotic-resistant bacteria can occur at extremely low antibiotic concentrations, similar to those concentrations found in some aquatic and soil environments, showing that even these concentrations of antibiotics may promote antibiotic resistance. However, the mechanisms contributing to antibiotic resistance have been partially explored in environmental settings. This WP will determine whether human disturbance may promote the transfer of ARGs via phages within microbial communities.
WP2 – Establishing the potential gene transfer via phages among bacteria.
Considering that phages are the most abundant and diverse biological entities in the planet, and they have the potential to transfer genetic material between bacterial hosts, the recruitment of novel genes carried by phages, or the alteration of expression patterns of already existing genes can confer beneficial phenotypic traits that allow adaptation to adverse conditions (e.g. pollution). Therefore, the role of phages deserves special attention considering the wide array of mechanisms by which ARGs may spread among bacteria and eventually to human pathogens. The results of this research are expected to provide clues for a better understanding of the evolutionary pathways through which antibiotic resistance determinants spread within natural microbial communities and how they are introduced into clinically-relevant pathogens.
WP3 – Elucidating bacterium-phage interactions (months 16–23)
In this WP, we will focus on how bacterial communities adapt and/or respond to the presence of phages harbouring ARGs under stressful conditions, such as exposure to antibiotics and other pollutants (e.g. disinfectants and heavy metals). We will also examine whether and to what extent environmental factors (e.g. temperature and nutrient limitation) may affect gene transfer via phages among microbial communities.
One of the main hypotheses in PHASTER is that human perturbations can increase the prevalence of phages harbouring ARGs in the environment. Recent studies have suggested that selection of antibiotic-resistant bacteria can occur at extremely low antibiotic concentrations, similar to those concentrations found in some aquatic and soil environments, showing that even these concentrations of antibiotics may promote antibiotic resistance. However, the mechanisms contributing to antibiotic resistance have been partially explored in environmental settings. This WP will determine whether human disturbance may promote the transfer of ARGs via phages within microbial communities.
WP2 – Establishing the potential gene transfer via phages among bacteria.
Considering that phages are the most abundant and diverse biological entities in the planet, and they have the potential to transfer genetic material between bacterial hosts, the recruitment of novel genes carried by phages, or the alteration of expression patterns of already existing genes can confer beneficial phenotypic traits that allow adaptation to adverse conditions (e.g. pollution). Therefore, the role of phages deserves special attention considering the wide array of mechanisms by which ARGs may spread among bacteria and eventually to human pathogens. The results of this research are expected to provide clues for a better understanding of the evolutionary pathways through which antibiotic resistance determinants spread within natural microbial communities and how they are introduced into clinically-relevant pathogens.
WP3 – Elucidating bacterium-phage interactions (months 16–23)
In this WP, we will focus on how bacterial communities adapt and/or respond to the presence of phages harbouring ARGs under stressful conditions, such as exposure to antibiotics and other pollutants (e.g. disinfectants and heavy metals). We will also examine whether and to what extent environmental factors (e.g. temperature and nutrient limitation) may affect gene transfer via phages among microbial communities.
We believe that the PHASTER project will generate results with a direct impact on the scientific community, economic development, and society.
Expected scientific impact. This research project will provide a better understanding of the contribution of phages to the acquisition and spread of ARGs and their interaction with antibiotic compounds, even at extremely low concentrations. This is because exposure of antibiotic-resistant bacteria to stressors of anthropogenic origin may trigger gene transfer between bacteria via mobile genetic elements (e.g. phages). This warrants further studies to elucidate to what extent phage-mediated gene transfer contributes to antibiotic resistance and what preventive measures should be implemented to mitigate this potential risk. Thus, the high-quality scientific publications and outreach activities foreseen in this project will promote and strengthen the establishment of public and environmental health strategies and mitigation programs for reducing the impact of antibiotic resistance.
Expected economic/technological impact. Antibiotic resistance has become a global public health concern, which has developed over time, from resistance to single classes of antibiotics to multidrug resistance and extreme drug resistance, thereby increasing the challenge for the development of more effective antibiotics. According to the recent report from the Antimicrobial Resistance Collaborators, every year approximately 1.3 million deaths directly attributable to antibiotic resistance worldwide. Moreover, antibiotic resistance is responsible for costs about 1.1 billion Euros to the health care system of European countries. Therefore, the role of phages deserves special attention considering the wide array of mechanisms by which ARGs may spread among bacteria and eventually to human pathogens. The results of this research are expected to provide clues for a better understanding of the evolutionary pathways through which antibiotic resistance determinants spread within microbial communities.
Expected societal impact. This project will make a significant and tangible contribution towards the mechanisms and pathways by which antibiotic resistance evolves and spreads, which will permit the implementation of appropriate public health strategies, policies, and mitigation programs for reducing their impact on the public and environmental health. If it is successful, this project will have future tangible impacts on the overall human and environmental health by providing information on to what extent phage-mediated gene transfer contributes to antibiotic resistance, as well as on what factors facilitate this gene transfer. In this context, the main goal of PHASTER is to contribute to achieving the objectives of the European One Health Action Plan against antibiotic resistance and the WHO Global Action Plan on antibiotic resistance, which are aimed at reducing the impact of this phenomenon on human, animal, and environmental health.
Expected scientific impact. This research project will provide a better understanding of the contribution of phages to the acquisition and spread of ARGs and their interaction with antibiotic compounds, even at extremely low concentrations. This is because exposure of antibiotic-resistant bacteria to stressors of anthropogenic origin may trigger gene transfer between bacteria via mobile genetic elements (e.g. phages). This warrants further studies to elucidate to what extent phage-mediated gene transfer contributes to antibiotic resistance and what preventive measures should be implemented to mitigate this potential risk. Thus, the high-quality scientific publications and outreach activities foreseen in this project will promote and strengthen the establishment of public and environmental health strategies and mitigation programs for reducing the impact of antibiotic resistance.
Expected economic/technological impact. Antibiotic resistance has become a global public health concern, which has developed over time, from resistance to single classes of antibiotics to multidrug resistance and extreme drug resistance, thereby increasing the challenge for the development of more effective antibiotics. According to the recent report from the Antimicrobial Resistance Collaborators, every year approximately 1.3 million deaths directly attributable to antibiotic resistance worldwide. Moreover, antibiotic resistance is responsible for costs about 1.1 billion Euros to the health care system of European countries. Therefore, the role of phages deserves special attention considering the wide array of mechanisms by which ARGs may spread among bacteria and eventually to human pathogens. The results of this research are expected to provide clues for a better understanding of the evolutionary pathways through which antibiotic resistance determinants spread within microbial communities.
Expected societal impact. This project will make a significant and tangible contribution towards the mechanisms and pathways by which antibiotic resistance evolves and spreads, which will permit the implementation of appropriate public health strategies, policies, and mitigation programs for reducing their impact on the public and environmental health. If it is successful, this project will have future tangible impacts on the overall human and environmental health by providing information on to what extent phage-mediated gene transfer contributes to antibiotic resistance, as well as on what factors facilitate this gene transfer. In this context, the main goal of PHASTER is to contribute to achieving the objectives of the European One Health Action Plan against antibiotic resistance and the WHO Global Action Plan on antibiotic resistance, which are aimed at reducing the impact of this phenomenon on human, animal, and environmental health.