The all-intracellular order Legionellales is unexpectedly diverse, globally distributed and lowly abundant

Legionellales is an order of the Gammaproteobacteria, only composed of host-adapted, intracellular bacteria, including the accidental human pathogens Legionella pneumophila and Coxiella burnetii. Although the diversity in terms of lifestyle is large across the order, only a few genera have been sequenced, owing to the difficulty to grow intracellular bacteria in pure culture. In particular, we know little about their global distribution and abundance. Here, we analyze 16/18S rDNA amplicons both from tens of thousands of published studies and from two separate sampling campaigns in and around ponds and in a silver mine. We demonstrate that the diversity of the order is much larger than previously thought, with over 450 uncultured genera. We show that Legionellales are found in about half of the samples from freshwater, soil and marine environments and quasi-ubiquitous in man-made environments. Their abundance is low, typically 0.1%, with few samples up to 1%. Most Legionellales OTUs are globally distributed, while many do not belong to a previously identified species. This study sheds a new light on the ubiquity and diversity of one major group of host-adapted bacteria. It also emphasizes the need to use metagenomics to better understand the role of host-adapted bacteria in all environments. The all-intracellular bacterial order of Legionellales is much more diverse, prevalent and globally distributed than previously thought

Factors impacting antimicrobial resistance in the South East Asian food system and potential places to intervene: A participatory, one health study

BackgroundWith AMU projected to increase, South East Asia (SEA) is at high risk of experiencing disproportionate health, social, and economic burdens due to antimicrobial resistance (AMR). Our objective was to identify factors influencing AMR in SEA’s food system and places for intervention by integrating the perspectives of experts from the region to inform policy and management decisions.Materials and methodsWe conducted two 6.5 h workshops and two 90-min interviews involving 18 AMR and other disciplinary experts from human, animal, and environment sectors who brainstormed the factors influencing AMR and identified leverage points (places) for intervention. Transcripts and workshop materials were coded for factors and their connections and transcribed into a causal loop diagram (CLD). Thematic analysis described AMR dynamics in SEA’s food system and leverage points for intervention. The CLD and themes were confirmed via participant feedback.ResultsParticipants constructed a CLD of AMR in the SEA food system that contained 98 factors interlinked by 362 connections. CLD factors reflected eight sub-areas of the SEA food system (e.g., government). Seven themes [e.g., antimicrobial and pesticide use and AMR spread (n = 40 quotes)], six “overarching factors” that impact the entire AMR system [e.g., the drive to survive (n = 12 quotes)], and 10 places for intervention that target CLD factors (n = 5) and overarching factors (n = 2) emerged from workshop discussions.ConclusionThe participant derived CLD of factors influencing AMR in the SEA food system demonstrates that AMR is a product of numerous interlinked actions taken across the One Health spectrum and that finding solutions is no simple task. Developing the model enabled the identification of potentially promising leverage points across human, animal, and environment sectors that, if comprehensively targeted using multi-pronged interventions, could evoke system wide changes that mitigate AMR. Even targeting some leverage points for intervention, such as increasing investments in research and capacity building, and setting and enforcing regulations to control antimicrobial supply, demand, and use could, in turn, shift mindsets that lead to changes in more difficult to alter leverage points, such as redefining the profit-driven intent that drives system behavior in ways that transform AMU and sustainably mitigate AMR

Governing Antimicrobial Resistance (AMR) in a Changing Climate: A Participatory Scenario Planning Approach Applied to Sweden in 2050

Background: Antimicrobial resistance (AMR) is a growing global crisis with long-term and unpredictable health, social and economic impacts, with which climate change is likely to interact. Understanding how to govern AMR amidst evolving climatic changes is critical. Scenario planning offers a suitable approach. By envisioning alternative futures, stakeholders more effectively can identify consequences, anticipate problems, and better determine how to intervene. This study explored future worlds and actions that may successfully address AMR in a changing climate in a high-income country, using Sweden as the case.Methods: We conducted online scenario-building workshops and interviews with eight experts who explored: (1) how promising interventions (taxation of antimicrobials at point of sale, and infection prevention measures) could each combat AMR in 2050 in Sweden given our changing climate; and (2) actions to take starting in 2030 to ensure success in 2050. Transcripts were thematically analyzed to produce a narrative of participant validated alternative futures.Results: Recognizing AMR to be a global problem requiring global solutions, participants looked beyond Sweden to construct three alternative futures: (1) “Tax Burn Out” revealed taxation of antimicrobials as a low-impact intervention that creates inequities and thus would fail to address AMR without other interventions, such as infection prevention measures. (2) “Addressing the Basics” identified infection prevention measures as highly impactful at containing AMR in 2050 because they would contribute to achieving the Sustainable Development Goals (SDGs), which would be essential to tackling inequities underpinning AMR and climate change, and help to stabilize climate-induced mass migration and conflicts; and (3) ”Siloed Nations” described a movement toward nationalism and protectionism that would derail the “Addressing the Basics” scenario, threatening health and wellbeing of all. Several urgent actions were identified to combat AMR long-term regardless which future un-folds, such as global collaboration, and a holistic approach where AMR and climate change are addressed as interlinked issues.Conclusion: Our participatory scenario planning approach enabled participants from different sectors to create shared future visions and identify urgent actions to take that hinge on global collaboration, addressing AMR and climate change together, and achieving the SDGs to combat AMR under a changing climate

Factors influencing antimicrobial resistance in the European food system and potential leverage points for intervention: A participatory, One Health study

Introduction Antimicrobial resistance (AMR) is a global crisis that evolves from a complex system of factors. Understanding what factors interact is key to finding solutions. Our objective was to identify the factors influencing AMR in the European food system and places to intervene. Materials and methods We conducted two workshops involving participants with diverse perspectives to identify the factors influencing AMR and leverage points (places) to target interventions. Transcripts were open coded for factors and connections, then transcribed into Vensim 8.0.4 to develop a causal loop diagram (CLD) and compute the number of feedback loops. Thematic analysis followed to describe AMR dynamics in Europe’s food system and places for intervention. The CLD and themes were confirmed via participant feedback. Results Seventeen participants representing human, animal and agricultural sectors identified 91 CLD factors and 331 connections. Seven themes (e.g., social and economic conditions) describing AMR dynamics in Europe’s food system, five ‘overarching factors’ that impact the entire CLD system (e.g., leadership) and fourteen places for intervention (e.g., consumer demand) emerged from workshop discussions. Most leverage points fell on highly networked feedback loops suggesting that intervening at these places may create unpredictable consequences. Conclusions Our study produced a CLD of factors influencing AMR in Europe’s food system that implicates sectors across the One Health spectrum. The high connectivity between the CLD factors described by participants and our finding that factors are connected with many feedback mechanisms underscores the complexity of the AMR problem and the challenge with finding long-term solutions. Identifying factors and feedbacks helped identify relevant leverage points in the system. Some actions, such as government’s setting AMU standards may be easier to implement. These actions in turn can support multi-pronged actions that can help redefine the vision, values and goals of the system to sustainably tackle AMR

Studying Factors Affecting Success of Antimicrobial Resistance Interventions through the Lens of Experience: A Thematic Analysis

Antimicrobial resistance (AMR) affects the environment, and animal and human health. Institutions worldwide have applied various measures, some of which have reduced antimicrobial use and AMR. However, little is known about factors influencing the success of AMR interventions. To address this gap, we engaged health professionals, designers, and implementers of AMR interventions in an exploratory study to learn about their experience and factors that challenged or facilitated interventions and the context in which interventions were implemented. Based on participant input, our thematic analysis identified behaviour; institutional governance and management; and sharing and enhancing information as key factors influencing success. Important sub-themes included: correct behaviour reinforcement, financial resources, training, assessment, and awareness of AMR. Overall, interventions were located in high-income countries, the human sector, and were publicly funded and implemented. In these contexts, behaviour patterns strongly influenced success, yet are often underrated or overlooked when designing AMR interventions. Improving our understanding of what contributes to successful interventions would allow for better designs of policies that are tailored to specific contexts. Exploratory approaches can provide encouraging results in complex challenges, as made evident in our study. Remaining challenges include more engagement in this type of study by professionals and characterisation of themes that influence intervention outcomes by context

Antibiotic consumption was associated with higher abundance of gut microbiota species previously linked to coronary atherosclerosis in the population-based SCAPIS cohort

Background: The human gut microbiota is the complex microbial community that lives in our gut. The gut microbiota has a key role in health and disease and its disruption has been linked to several chronic diseases such as cardiovascular diseases. As antibiotics are well known disruptors of gut microbiota, the aim of this thesis work was to identify associations between previous antibiotic consumption and the abundance of seven gut microbiota species previously linked to subclinical coronary atherosclerosis in the large population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort. Materials and Methods: Faecal samples of 9,794 individuals from the SCAPIS Uppsala and Malmö cohorts were analysed by deep shotgun metagenomics sequencing in a cross-sectional study. Previous antibiotic use was retrieved using the Swedish Drug Prescribed Register and divided into three periods: one year, between one and five years, and between five and nine years before faecal sampling. Associations between antibiotic consumption and the gut microbiota species were evaluated using linear regression adjusted for covariates and corrected for multiple testing. Results: Our results showed that antibiotic consumption was associated with an increased abundance of Ligilactobacillus salivarius, Bifidobacterium dentium, Rothia mucilaginosa, Streptococcus parasanguinis and Streptococcus oralis subsp. oralis. Often these positive associations were present for antibiotic consumed between one and five years before sampling.  The strongest associations were for broad-spectrum antibiotics and lincosamides with L. salivarius, B. dentium, R. mucilaginosa and S. parasanguinis; and for nitrofurantoin with S. oralis subsp. oralis.   Conclusions: This study provides insights on how antibiotic consumption is associated with enrichment and higher abundance of species previously linked with subclinical coronary atherosclerosis in the gut. Hence, this study provides insights on unintended effects of using antibiotics for managing infections, which underscores antibiotic use as not only a concern for development of antibiotic resistance but also for disrupting the gut microbiota, which may contribute to disease development. Knowledge about effect of antibiotics in gut microbiota may help to adequate this therapy according to comorbidities of individual profiles and to design better diagnostic tools for the risk population with the goal of preventing cardiovascular events in the general population.

Antibiotic consumption was associated with higher abundance of gut microbiota species previously linked to coronary atherosclerosis in the population-based SCAPIS cohort

Background: The human gut microbiota is the complex microbial community that lives in our gut. The gut microbiota has a key role in health and disease and its disruption has been linked to several chronic diseases such as cardiovascular diseases. As antibiotics are well known disruptors of gut microbiota, the aim of this thesis work was to identify associations between previous antibiotic consumption and the abundance of seven gut microbiota species previously linked to subclinical coronary atherosclerosis in the large population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort. Materials and Methods: Faecal samples of 9,794 individuals from the SCAPIS Uppsala and Malmö cohorts were analysed by deep shotgun metagenomics sequencing in a cross-sectional study. Previous antibiotic use was retrieved using the Swedish Drug Prescribed Register and divided into three periods: one year, between one and five years, and between five and nine years before faecal sampling. Associations between antibiotic consumption and the gut microbiota species were evaluated using linear regression adjusted for covariates and corrected for multiple testing. Results: Our results showed that antibiotic consumption was associated with an increased abundance of Ligilactobacillus salivarius, Bifidobacterium dentium, Rothia mucilaginosa, Streptococcus parasanguinis and Streptococcus oralis subsp. oralis. Often these positive associations were present for antibiotic consumed between one and five years before sampling.  The strongest associations were for broad-spectrum antibiotics and lincosamides with L. salivarius, B. dentium, R. mucilaginosa and S. parasanguinis; and for nitrofurantoin with S. oralis subsp. oralis.   Conclusions: This study provides insights on how antibiotic consumption is associated with enrichment and higher abundance of species previously linked with subclinical coronary atherosclerosis in the gut. Hence, this study provides insights on unintended effects of using antibiotics for managing infections, which underscores antibiotic use as not only a concern for development of antibiotic resistance but also for disrupting the gut microbiota, which may contribute to disease development. Knowledge about effect of antibiotics in gut microbiota may help to adequate this therapy according to comorbidities of individual profiles and to design better diagnostic tools for the risk population with the goal of preventing cardiovascular events in the general population.

The Anthropocene Operating Space for antimicrobial resistance: tipping points in treatability of priority pathogens

Evolution of antimicrobial resistance, especially antibiotic resistance, results from complex dynamics between microorganisms, stressors and the environment itself, where non-linear dynamics are present with unpredictable impacts on treatability, and therefore, on society. The Anthropocene Operating Space for Antimicrobial Resistance is a recent framework for risk-assessment of tipping-points in treatability by combining information about the level of resistance and the effects of available antimicrobials. Here, we develop this framework at an increased level of resolution and extent compared to previous analysis adding three sub-zones to the original three zone framework and applying it to 20 priority pathogens, constituting its first application at the pathogen level, including fungal pathogens. In doing so, we also provide updated definitions of each zone and sub-zone together with an overview of mechanisms and contexts contributing to treatability of tipping point risks. We find that 7 out of 20 assessed priority pathogens (6 out of 11 Gram-negative bacteria) are in the zone of highest risk where widespread tipping points in treatability are most likely (surpassed zone). Namely, Acinetobacter spp., Pseudomonas spp., Enterobacteriaceae (Escherichia coli and Klebsiella pneumoniae), Neisseria gonorrhoeae and the yeast Candida auris are those assessed exceeding our current resources. Meanwhile, Mycobacterium tuberculosis, Clostridioides difficile, Staphylococcus aureus, Enterococcus and Salmonella are classified at very high risk of crossing the tipping point in treatability. The problem of antimicrobial resistance is often described as a future threat in the so-called post-antibiotic era. However, our assessment concludes we may have surpassed the threshold in some of the scenarios, and that we are on the edge in others. The proposed framework, being easy to implement across sectors, while requiring little or no economic investment, unifies criteria to be used between different key actors joining two important parameters in antimicrobial resistance: the epidemiological state of priority pathogens and treatment sustainability. In the future the framework can be expanded to other pathogens and repeated assessments will be useful as an indicator of tracking trends in treatability tipping-point risks

The all-intracellular order Legionellales is unexpectedly diverse, globally distributed and lowly abundant

Legionellales is an order of the Gammaproteobacteria, only composed of host-adapted, intracellular bacteria, including the accidental human pathogens Legionella pneumophila and Coxiella burnetii. Although the diversity in terms of lifestyle is large across the order, only a few genera have been sequenced, owing to the difficulty to grow intracellular bacteria in pure culture. In particular, we know little about their global distribution and abundance. Here, we analyze 16/18S rDNA amplicons both from tens of thousands of published studies and from two separate sampling campaigns in and around ponds and in a silver mine. We demonstrate that the diversity of the order is much larger than previously thought, with over 450 uncultured genera. We show that Legionellales are found in about half of the samples from freshwater, soil and marine environments and quasi-ubiquitous in man-made environments. Their abundance is low, typically 0.1%, with few samples up to 1%. Most Legionellales OTUs are globally distributed, while many do not belong to a previously identified species. This study sheds a new light on the ubiquity and diversity of one major group of host-adapted bacteria. It also emphasizes the need to use metagenomics to better understand the role of host-adapted bacteria in all environments. The all-intracellular bacterial order of Legionellales is much more diverse, prevalent and globally distributed than previously thought

Characterising proximal and distal drivers of antimicrobial resistance: An umbrella review

Introduction: Antimicrobial resistance (AMR) is a multifactorial challenge driven by a complex interplay of proximal drivers, such as the overuse and misuse of antimicrobials and the high burden of infectious diseases, and distal factors, encompassing broader societal conditions such as poverty, inadequate sanitation, and healthcare system deficiencies. However, distinguishing between proximal and distal drivers remains a conceptual challenge. Objectives: We conducted an umbrella review, aiming to systematically map current evidence about proximal and distal drivers of AMR and to investigate their relationships. Methods: Forty-seven reviews were analysed, and unique causal links were retained to construct a causality network of AMR. To distinguish between proximal and distal drivers, we calculated a ‘driver distalness index (Di)’, defined as an average relative position of a driver in its causal pathways to AMR. Results: The primary emphasis of the literature remained on proximal drivers, with fragmented existing evidence about distal drivers. The network analysis showed that proximal drivers of AMR are associated with risks of resistance transmission (Di = 0.49, SD = 0.14) and antibiotic use (Di = 0.58, SD = 0.2), which are worsened by intermediate drivers linked with challenges of antibiotic discovery (Di = 0.62, SD = 0.07), infection prevention (Di = 0.67, SD = 0.14) and surveillance (Di = 0.69, SD = 0.16). Distal drivers, such as living conditions, access to sanitation infrastructure, population growth and urbanisation, and gaps in policy implementation were development and governance challenges, acting as deep leverage points in the system in addressing AMR. Conclusions: Comprehensive AMR strategies aiming to address multiple chronic AMR challenges must take advantage of opportunities for upstream interventions that specifically address distal drivers