Evolution, Medicine, and Public Health最新文献

{"title":"COVID-19 and <i>Evolution, Medicine, and Public Health</i>.","authors":"Charles L Nunn","doi":"10.1093/emph/eoad002","DOIUrl":"https://doi.org/10.1093/emph/eoad002","url":null,"abstract":"According to the World Health Organization, 6.7 million people have died from COVID19 as of the start of 2023. These deaths are tragic with many societal ramifications. For example, more than 10 million children have lost caregivers globally through 1 May 2022 [1], while many others have suffered dramatic losses in educational attainment [2]. At times, the pandemic has overwhelmed healthcare services that have resulted in additional non-COVID death and suffering. COVID-19 has also caused sharp declines in mental health, particularly among children and adolescents [3, 4]. Mental disorders, such as depression and anxiety, are often debilitating and long-lasting, thus contributing greatly to years lived with disability. Some bright spots have also occurred, including the marked reduction in deaths due to influenza in the first year of the pandemic due to masking and social isolation and the rapid rollout of vaccines using new technologies such as mRNA vaccines, which offer great promise in battling other infectious diseases. One lesson from the pandemic is the importance of interdisciplinary approaches for addressing complex problems. We cannot control a viral pandemic with just virology. We need epidemiologists, engineers, sociologists, political scientists, historians, medical doctors, economists, statisticians, anthropologists, mathematicians and geographers (among others!) to comprehend the interconnections of human behavior, disease transmission, government interventions, global transport and trade, and the production and distribution of vaccines and treatments. Evolutionary biology is another field that has been crucial for making sense of the COVID-19 pandemic. Examples of evolutionary biology’s importance are many, including identifying selective pressures that lead to the rise of new variants of concern, understanding human responses to disease in relation to past evolutionary pressures from other infectious diseases, and investigating the breadth of hosts that coronaviruses infect and the ecological context of their spillover among hosts. In many cases, these evolutionary perspectives are also crucial to mitigation efforts. For example, phylogenetic approaches can reveal the origins of a new human pathogen from other species, helping guide surveillance efforts in wildlife or domesticated animals, while also revealing transmission pathways among human populations. In the early months of the pandemic, for example, many of us spent hours on NextStrain (https:// nextstrain.org/) examining the most up-to-date phylogenies of SARS-CoV-2 to help make sense of its global movement. We can see the breadth of these evolutionary perspectives on COVID-19 in the pages of Evolution, Medicine, and Public Health (EMPH). So far, EMPH has published 24 scientific articles EDITORIAL BY INVITATION ONLY","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"11 1","pages":"41-43"},"PeriodicalIF":3.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9993055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9642505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-pharmaceutical interventions and the emergence of pathogen variants.","authors":"Ben Ashby, Cameron A Smith, Robin N Thompson","doi":"10.1093/emph/eoac043","DOIUrl":"10.1093/emph/eoac043","url":null,"abstract":"<p><p>Non-pharmaceutical interventions (NPIs), such as social distancing and contact tracing, are important public health measures that can reduce pathogen transmission. In addition to playing a crucial role in suppressing transmission, NPIs influence pathogen evolution by mediating mutation supply, restricting the availability of susceptible hosts, and altering the strength of selection for novel variants. Yet it is unclear how NPIs might affect the emergence of novel variants that are able to escape pre-existing immunity (partially or fully), are more transmissible or cause greater mortality. We analyse a stochastic two-strain epidemiological model to determine how the strength and timing of NPIs affect the emergence of variants with similar or contrasting life-history characteristics to the wild type. We show that, while stronger and timelier NPIs generally reduce the likelihood of variant emergence, it is possible for more transmissible variants with high cross-immunity to have a greater probability of emerging at intermediate levels of NPIs. This is because intermediate levels of NPIs allow an epidemic of the wild type that is neither too small (facilitating high mutation supply), nor too large (leaving a large pool of susceptible hosts), to prevent a novel variant from becoming established in the host population. However, since one cannot predict the characteristics of a variant, the best strategy to prevent emergence is likely to be an implementation of strong, timely NPIs.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"11 1","pages":"80-89"},"PeriodicalIF":3.3,"publicationDate":"2022-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9234396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sound reasons for unsound sleep: Comparative support for the sentinel hypothesis in industrial and nonindustrial groups.","authors":"Leela McKinnon, Eric C Shattuck, David R Samson","doi":"10.1093/emph/eoac039","DOIUrl":"10.1093/emph/eoac039","url":null,"abstract":"<p><strong>Background and objectives: </strong>Sleep is a vulnerable state in which individuals are more susceptible to threat, which may have led to evolved mechanisms for increasing safety. The sentinel hypothesis proposes that brief awakenings during sleep may be a strategy for detecting and responding to environmental threats. Observations of sleep segmentation and group sentinelization in hunter-gatherer and small-scale communities support this hypothesis, but to date it has not been tested in comparisons with industrial populations characterized by more secure sleep environments.</p><p><strong>Methodology: </strong>Here, we compare wake after sleep onset (WASO), a quantitative measure of nighttime awakenings, between two nonindustrial and two industrial populations: Hadza hunter-gatherers (<i>n</i> = 33), Malagasy small-scale agriculturalists (<i>n</i> = 38), and Hispanic (<i>n</i> = 1,531) and non-Hispanic White (NHW) (<i>n</i> = 347) Americans. We compared nighttime awakenings between these groups using actigraphically-measured sleep data. We fit linear models to assess whether WASO varies across groups, controlling for sex and age.</p><p><strong>Results: </strong>We found that WASO varies significantly by group membership and is highest in Hadza (2.44 h) and Malagasy (1.93 h) and lowest in non-Hispanic Whites (0.69 h). Hispanics demonstrate intermediate WASO (0.86 h), which is significantly more than NHW participants. After performing supplementary analysis within the Hispanic sample, we found that WASO is significantly and positively associated with increased perception of neighborhood violence.</p><p><strong>Conclusions and implications: </strong>Consistent with principles central to evolutionary medicine, we propose that evolved mechanisms to increase vigilance during sleep may now be mismatched with relatively safer environments, and in part responsible for driving poor sleep health.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"11 1","pages":"53-66"},"PeriodicalIF":3.7,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9215093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigenic evolution of SARS-CoV-2 in immunocompromised hosts.","authors":"Cameron A Smith, Ben Ashby","doi":"10.1093/emph/eoac037","DOIUrl":"10.1093/emph/eoac037","url":null,"abstract":"<p><strong>Objectives/aims: </strong>Prolonged infections of immunocompromised individuals have been proposed as a crucial source of new variants of SARS-CoV-2 during the COVID-19 pandemic. In principle, sustained within-host antigenic evolution in immunocompromised hosts could allow novel immune escape variants to emerge more rapidly, but little is known about how and when immunocompromised hosts play a critical role in pathogen evolution.</p><p><strong>Materials and methods: </strong>Here, we use a simple mathematical model to understand the effects of immunocompromised hosts on the emergence of immune escape variants in the presence and absence of epistasis.</p><p><strong>Conclusions: </strong>We show that when the pathogen does not have to cross a fitness valley for immune escape to occur (no epistasis), immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level (epistasis), then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore, facilitating rather than simply speeding up antigenic evolution. Our results suggest that better genomic surveillance of infected immunocompromised individuals and better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"11 1","pages":"90-100"},"PeriodicalIF":3.3,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10061940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9240283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life adversity, reproductive history and breast cancer risk.","authors":"Amy M Boddy, Shawn Rupp, Zhe Yu, Heidi Hanson, Athena Aktipis, Ken Smith","doi":"10.1093/emph/eoac034","DOIUrl":"10.1093/emph/eoac034","url":null,"abstract":"<p><strong>Background and objectives: </strong>Individuals who experience early life adversity are at an increased risk for chronic disease later in life. Less is known about how early life factors are associated with cancer susceptibility. Here, we use a life history framework to test whether early life adversity increases the risk of breast cancer. We predict that early life adversity can shift investment in somatic maintenance and accelerate the timing of reproduction, which may mediate or interact with the risk of breast cancer.</p><p><strong>Methodology: </strong>We use population-wide data from the Utah Population Database (UPDB) and Utah Cancer Registry, leading to 24 957 cases of women diagnosed with breast cancer spanning 20 years (1990-2010) and 124 785 age-matched controls. We generated a cumulative early life adversity summation score to evaluate the interaction (moderation) and mediation between early life adversity, reproductive history and their association with breast cancer risk.</p><p><strong>Results: </strong>Our analyses led to three key findings: (i) more early life adversity, when considered as a main effect, accelerates the time to first birth and death, (ii) early age at first birth and high parity decreases the risk of breast cancer and (iii) we find no association between early adversity and breast cancer risk either as a main effect or in its interaction with reproductive history.</p><p><strong>Conclusion and implications: </strong>Early adversity elevates the risk of overall mortality through mechanisms other than breast cancer risk. This suggests early life factors can generate different effects on health. Future work should incorporate more complex view of life history patterns, including multiple life stages, when making predictions about cancer susceptibility.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"429-438"},"PeriodicalIF":3.7,"publicationDate":"2022-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9953211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of leg length for metabolic health and fitness.","authors":"Meghan K Shirley, Owen J Arthurs, Kiran K Seunarine, Tim J Cole, Simon Eaton, Jane E Williams, Chris A Clark, Jonathan C K Wells","doi":"10.1093/emph/eoac023","DOIUrl":"10.1093/emph/eoac023","url":null,"abstract":"<p><strong>Background and objectives: </strong>Several studies have linked longer legs with favorable adult metabolic health outcomes and greater offspring birth weight. A recent Mendelian randomization study suggested a causal link between height and cardiometabolic risk; however, the underlying reasons remain poorly understood.</p><p><strong>Methodology: </strong>Using a cross-sectional design, we tested in a convenience sample of 70 healthy young women whether birth weight and tibia length as markers of early-life conditions associated more strongly with metabolically beneficial traits like organ size and skeletal muscle mass (SMM) than a statistically derived height-residual variable indexing later, more canalized growth.</p><p><strong>Results: </strong>Consistent with the 'developmental origins of health and disease' hypothesis, we found relatively strong associations of tibia length-but not birth weight-with adult organ size, brain size, SMM and resting energy expenditure measured by magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry and indirect calorimetry, respectively.</p><p><strong>Conclusions and implications: </strong>Building on prior work, these results suggest that leg length is a sensitive marker of traits directly impacting metabolic and reproductive health. Alongside findings in the same sample relating tibia length and height-residual to MRI-measured pelvic dimensions, we suggest there may exist a degree of coordination in the development of long bone, lean mass and pelvic traits, possibly centered on early, pre-pubertal growth periods. Such phenotypic coordination has important implications for fitness, serving to benefit both adult health and the health of offspring in subsequent generations.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"316-324"},"PeriodicalIF":3.7,"publicationDate":"2022-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10701439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolved resistance to a novel cationic peptide antibiotic requires high mutation supply.","authors":"Alfonso Santos-Lopez, Melissa J Fritz, Jeffrey B Lombardo, Ansen H P Burr, Victoria A Heinrich, Christopher W Marshall, Vaughn S Cooper","doi":"10.1093/emph/eoac022","DOIUrl":"10.1093/emph/eoac022","url":null,"abstract":"<p><strong>Background and objectives: </strong>A key strategy for resolving the antibiotic resistance crisis is the development of new drugs with antimicrobial properties. The engineered cationic antimicrobial peptide WLBU2 (also known as PLG0206) is a promising broad-spectrum antimicrobial compound that has completed Phase I clinical studies. It has activity against Gram-negative and Gram-positive bacteria including infections associated with biofilm. No definitive mechanisms of resistance to WLBU2 have been identified.</p><p><strong>Methodology: </strong>Here, we used experimental evolution under different levels of mutation supply and whole genome sequencing (WGS) to detect the genetic pathways and probable mechanisms of resistance to this peptide. We propagated populations of wild-type and hypermutator <i>Pseudomonas aeruginosa</i> in the presence of WLBU2 and performed WGS of evolved populations and clones.</p><p><strong>Results: </strong>Populations that survived WLBU2 treatment acquired a minimum of two mutations, making the acquisition of resistance more difficult than for most antibiotics, which can be tolerated by mutation of a single target. Major targets of resistance to WLBU2 included the <i>orfN</i> and <i>pmrB</i> genes, previously described to confer resistance to other cationic peptides. More surprisingly, mutations that increase aggregation such as the <i>wsp</i> pathway were also selected despite the ability of WLBU2 to kill cells growing in a biofilm.</p><p><strong>Conclusions and implications: </strong>The results show how experimental evolution and WGS can identify genetic targets and actions of new antimicrobial compounds and predict pathways to resistance of new antibiotics in clinical practice.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"266-276"},"PeriodicalIF":3.3,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Which 'imperfect vaccines' encourage the evolution of higher virulence?","authors":"James J Bull, Rustom Antia","doi":"10.1093/emph/eoac015","DOIUrl":"10.1093/emph/eoac015","url":null,"abstract":"<p><strong>Background and objectives: </strong>Theory suggests that some types of vaccines against infectious pathogens may lead to the evolution of variants that cause increased harm, particularly when they infect unvaccinated individuals. This theory was supported by the observation that the use of an imperfect vaccine to control Marek's disease virus in chickens resulted in the virus evolving to be more lethal to unvaccinated birds. This raises the concern that the use of some other vaccines may lead to similar pernicious outcomes. We examine that theory with a focus on considering the regimes in which such outcomes are expected.</p><p><strong>Methodology: </strong>We evaluate the plausibility of assumptions in the original theory. The previous theory rested heavily on a particular form of transmission-mortality-recovery trade-off and invoked other assumptions about the pathways of evolution. We review alternatives to mortality in limiting transmission and consider evolutionary pathways that were omitted in the original theory.</p><p><strong>Results: </strong>The regime where the pernicious evolutionary outcome occurs is narrowed by our analysis but remains possible in various scenarios. We propose a more nuanced consideration of alternative models for the within-host dynamics of infections and for factors that limit virulence. Our analysis suggests imperfect vaccines against many pathogens will not lead to the evolution of pathogens with increased virulence in unvaccinated individuals.</p><p><strong>Conclusions and implications: </strong>Evolution of greater pathogen mortality driven by vaccination remains difficult to predict, but the scope for such outcomes appears limited. Incorporation of mechanistic details into the framework, especially regarding immunity, may be requisite for prediction accuracy.</p><p><strong>Lay summary: </strong>A virus of chickens appears to have evolved high mortality in response to a vaccine that merely prevented disease symptoms. Theory has predicted this type of evolution in response to a variety of vaccines and other interventions such as drug treatment. Under what circumstances is this pernicious result likely to occur? Analysis of the theory in light of recent changes in our understanding of viral biology raises doubts that medicine-driven, pernicious evolution is likely to be common. But we are far from a mechanistic understanding of the interaction between pathogen and host that can predict when vaccines and other medical interventions will lead to the unwanted evolution of more virulent pathogens. So, while the regime where a pernicious result obtains may be limited, caution remains warranted in designing many types of interventions.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"202-213"},"PeriodicalIF":3.3,"publicationDate":"2022-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9381216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolution of the human healthcare system and implications for understanding our responses to COVID-19.","authors":"Sharon E Kessler, Robert Aunger","doi":"10.1093/emph/eoac004","DOIUrl":"10.1093/emph/eoac004","url":null,"abstract":"<p><p>The COVID-19 pandemic has revealed an urgent need for a comprehensive, multidisciplinary understanding of how healthcare systems respond successfully to infectious pathogens-and how they fail. This study contributes a novel perspective that focuses on the selective pressures that shape healthcare systems over evolutionary time. We use a comparative approach to trace the evolution of care-giving and disease control behaviours across species and then map their integration into the contemporary human healthcare system. Self-care and pro-health environmental modification are ubiquitous across animals, while derived behaviours like care for kin, for strangers, and group-level organizational responses have evolved via different selection pressures. We then apply this framework to our behavioural responses to COVID-19 and demonstrate that three types of conflicts are occurring: (1) conflicting selection pressures on individuals, (2) evolutionary mismatches between the context in which our healthcare behaviours evolved and our globalized world of today and (3) evolutionary displacements in which older forms of care are currently dispensed through more derived forms. We discuss the significance of understanding how healthcare systems evolve and change for thinking about the role of healthcare systems in society during and after the time of COVID-19-and for us as a species as we continue to face selection from infectious diseases.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"87-107"},"PeriodicalIF":3.3,"publicationDate":"2022-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10265044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An orally administered drug prevents selection for antibiotic-resistant bacteria in the gut during daptomycin therapy.","authors":"Valerie J Morley,&nbsp;Derek G Sim,&nbsp;Aline Penkevich,&nbsp;Robert J Woods,&nbsp;Andrew F Read","doi":"10.1093/emph/eoac035","DOIUrl":"https://doi.org/10.1093/emph/eoac035","url":null,"abstract":"<p><strong>Background and objectives: </strong>Previously, we showed proof-of-concept in a mouse model that oral administration of cholestyramine prevented enrichment of daptomycin-resistant <i>Enterococcus faecium</i> in the gastrointestinal (GI) tract during daptomycin therapy. Cholestyramine binds daptomycin in the gut, which removes daptomycin selection pressure and so prevents the enrichment of resistant clones. Here, we investigated two open questions related to this approach: (i) can cholestyramine prevent the enrichment of diverse daptomycin mutations emerging <i>de novo</i> in the gut? and (ii) how does the timing of cholestyramine administration impact its ability to suppress resistance?</p><p><strong>Methodology: </strong>Mice with GI <i>E. faecium</i> were treated with daptomycin with or without cholestyramine, and <i>E. faecium</i> was cultured from feces to measure changes in daptomycin susceptibility. A subset of clones was sequenced to investigate the genomic basis of daptomycin resistance.</p><p><strong>Results: </strong>Cholestyramine prevented the enrichment of diverse resistance mutations that emerged <i>de novo</i> in daptomycin-treated mice. Whole-genome sequencing revealed that resistance emerged through multiple genetic pathways, with most candidate resistance mutations observed in the <i>clsA</i> gene. In addition, we observed that cholestyramine was most effective when administration started prior to the first dose of daptomycin. However, beginning cholestyramine after the first daptomycin dose reduced the frequency of resistant <i>E. faecium</i> compared to not using cholestyramine at all.</p><p><strong>Conclusions and implications: </strong>Cholestyramine prevented the enrichment of diverse daptomycin-resistance mutations in intestinal <i>E. faecium</i> populations during daptomycin treatment, and it is a promising tool for managing the transmission of daptomycin-resistant <i>E. faecium</i>.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"439-446"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9472784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10336334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}