Vibrio cholerae's mysterious Seventh Pandemic island (VSP-II) encodes novel Zur-regulated zinc starvation genes involved in chemotaxis and cell congregation.

Vibrio cholerae is the causative agent of cholera, a notorious diarrheal disease that is typically transmitted via contaminated drinking water. The current pandemic agent, the El Tor biotype, has undergone several genetic changes that include horizontal acquisition of two genomic islands (VSP-I and VSP-II). VSP presence strongly correlates with pandemicity; however, the contribution of these islands to V. cholerae's life cycle, particularly the 26-kb VSP-II, remains poorly understood. VSP-II-encoded genes are not expressed under standard laboratory conditions, suggesting that their induction requires an unknown signal from the host or environment. One signal that bacteria encounter under both host and environmental conditions is metal limitation. While studying V. cholerae's zinc-starvation response in vitro, we noticed that a mutant constitutively expressing zinc starvation genes (Δzur) congregates at the bottom of a culture tube when grown in a nutrient-poor medium. Using transposon mutagenesis, we found that flagellar motility, chemotaxis, and VSP-II encoded genes were required for congregation. The VSP-II genes encode an AraC-like transcriptional activator (VerA) and a methyl-accepting chemotaxis protein (AerB). Using RNA-seq and lacZ transcriptional reporters, we show that VerA is a novel Zur target and an activator of the nearby AerB chemoreceptor. AerB interfaces with the chemotaxis system to drive oxygen-dependent congregation and energy taxis. Importantly, this work suggests a functional link between VSP-II, zinc-starved environments, and energy taxis, yielding insights into the role of VSP-II in a metal-limited host or aquatic reservoir.

Association of ACEI/ARB and statin prescribing patterns with mortality after Transcatheter Aortic Valve Replacement (TAVR): Findings from real-world claims data.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become the standard of care for most patients with severe aortic stenosis (AS), but the impact of medical therapy prescribing patterns on post-TAVR patients has not been thoroughly investigated. METHODS: We analyzed Optum claims data from 9,012 adults who received TAVR for AS (January 2014-December 2018). Pharmacy claims data were used to identify patients who filled ACEI/ARB and/or statin prescriptions during the study's 90-day landmark period post-TAVR. Kaplan-Meier and adjusted Cox Proportional Hazards models were used to evaluate the association of prescribing patterns with mortality during the 3-year follow-up period. Subgroup analyses were performed to examine the impact of 11 potential confounders on the observed associations. RESULTS: A significantly lower adjusted 3-year mortality was observed for patients with post-TAVR prescription for ACEI/ARBs (hazard ratio [HR] = 0.82, 95% confidence interval [CI] 0.74-0.91, P = .0003) and statins (HR = 0.85, 95% CI 0.77-0.94, P = .0018) compared to patients who did not fill prescriptions for these medications post-TAVR. Subgroup analyses revealed that the survival benefit associated with ACEI/ARB prescription was not affected by any of the potential confounding variables, except preoperative ACEI/ARB prescription was associated with significantly lower risk of mortality vs postoperative prescription only. No other subgroup variables had significant interactions associated with survival benefits, including preoperative use of statins. CONCLUSIONS: In this large-scale, real-world analysis of patients undergoing TAVR, the prescription of ACEI/ARB and statins was associated with a significantly lower risk of mortality at 3-years, especially in those where the medications were initiated preoperatively.

Outpatient visits before and after Lyme disease diagnosis in a Maryland employer-based health plan.

BACKGROUND: Insurance claims data have been used to inform an understanding of Lyme disease epidemiology and cost of care, however few such studies have incorporated post-treatment symptoms following diagnosis. Using longitudinal data from a private, employer-based health plan in an endemic US state, we compared outpatient care utilization pre- and post-Lyme disease diagnosis. We hypothesized that utilization would be higher in the post-diagnosis period, and that temporal trends would differ by age and gender. METHODS: Members with Lyme disease were required to have both a corresponding ICD-9 code and a fill of an antibiotic indicated for treatment of the infection within 30 days of diagnosis. A 2-year 'pre- diagnosis' period and a 2-year 'post-diagnosis period' were centered around the diagnosis month. Lyme disease-relevant outpatient care visits were defined as specific primary care, specialty care, or urgent care visits. Descriptive statistics examined visits during these pre- and post-diagnosis periods, and the association between these periods and the number of visits was explored using generalized linear mixed effects models adjusting for age, season of the year, and gender. RESULTS: The rate of outpatient visits increased 26% from the pre to the post-Lyme disease diagnosis periods among our 317-member sample (rate ratio = 1.26 [1.18, 1.36], p < 0.001). Descriptively, care utilization increases appeared to persist across months in the post-diagnosis period. Women's care utilization increased by 36% (1.36 [1.24, 1.50], p < 0.001), a significantly higher increase than the 14% increase found among men (1.14 [1.02, 1.27], p = 0.017). This gender difference was mainly driven by adult members. We found a borderline significant 17% increase in visits for children < 18 years, (1.17 [0.99, 1.38], p = 0.068), and a 31% increase for adults ≥ 18 years (1.31 [1.21, 1.42], p < 0.001). CONCLUSIONS: Although modest at the population level, the statistically significant increases in post-Lyme diagnosis outpatient care we observed were persistent and unevenly distributed across demographic and place of service categories. As Lyme disease cases continue to grow, so will the cumulative prevalence of persistent symptoms after treatment. Therefore, it will be important to confirm these findings and understand their significance for care utilization and cost, particularly against the backdrop of other post-acute infectious syndromes.

Structural basis of peptidoglycan endopeptidase regulation.

Most bacteria surround themselves with a cell wall, a strong meshwork consisting primarily of the polymerized aminosugar peptidoglycan (PG). PG is essential for structural maintenance of bacterial cells, and thus for viability. PG is also constantly synthesized and turned over; the latter process is mediated by PG cleavage enzymes, for example, the endopeptidases (EPs). EPs themselves are essential for growth but also promote lethal cell wall degradation after exposure to antibiotics that inhibit PG synthases (e.g., ß-lactams). Thus, EPs are attractive targets for novel antibiotics and their adjuvants. However, we have a poor understanding of how these enzymes are regulated in vivo, depriving us of novel pathways for the development of such antibiotics. Here, we have solved crystal structures of the LysM/M23 family peptidase ShyA, the primary EP of the cholera pathogen Vibrio cholerae Our data suggest that ShyA assumes two drastically different conformations: a more open form that allows for substrate binding and a closed form, which we predicted to be catalytically inactive. Mutations expected to promote the open conformation caused enhanced activity in vitro and in vivo, and these results were recapitulated in EPs from the divergent pathogens Neisseria gonorrheae and Escherichia coli Our results suggest that LysM/M23 EPs are regulated via release of the inhibitory Domain 1 from the M23 active site, likely through conformational rearrangement in vivo.

Genetic divergence among threespine stickleback that differ in nuptial coloration.

Sexual signals are shaped by their intended and unintended receivers as well as the signalling environment. This interplay between sexual and natural selection can lead to divergence in signals in heterogeneous environments. Yet, the extent to which gene flow is restricted when signalling phenotypes vary across environments and over what spatial scales remains an outstanding question. In this study, we quantify gene flow between two colour morphs, red and black, of freshwater threespine stickleback fish (Gasterosteus aculeatus). We capitalize on the very recent divergence of signalling phenotypes in this system to characterize within-species and among-morph genetic variation and to test for levels of gene flow between colour morphs in Oregon and Washington. Despite limited evidence for assortative mating between allopatric red and black populations, we found that black populations are genetically distinct from nearby red populations and that the black morph appears to have evolved independently at least twice in Oregon and Washington. Surprisingly, we uncovered a group of stickleback in one small coastal stream, Connor Creek, which is genetically and morphologically distinct from the red and black colour morphs and from marine stickleback. Historically, both colour morphs have coexisted in this location and sometimes hybridized, raising new questions about the origins and history of these fish, which were first described as anadromous-black hybrids >50 years ago. Understanding how genetic variation is currently partitioned within and among populations and colour morphs in this system should prompt future studies to assess the relative roles of habitat, ecological and pre- and post-reproductive barriers in the genetic divergence and phenotypic patterns we observe in nature.

Metabolomics-based mass spectrometry methods to analyze the chemical content of 3D organoid models.

Metabolomics, the study of metabolites present in biological samples, can provide a global view of sample state as well as insights into biological changes caused by disease or environmental interactions. Mass spectrometry (MS) is commonly used for metabolomics analysis given its high-throughput capabilities, high sensitivity, and capacity to identify multiple compounds in complex samples simultaneously. MS can be coupled to separation methods that can handle small volumes, making it well suited for analyzing the metabolome of organoids, miniaturized three-dimensional aggregates of stem cells that model in vivo organs. Organoids are being used in research efforts to study human disease and development, and in the design of personalized drug treatments. For organoid models to be useful, they need to recapitulate morphological and chemical aspects, such as the metabolome, of the parent tissue. This review highlights the separation- and imaging-based MS-based metabolomics methods that have been used to analyze the chemical contents of organoids. Future perspectives on how MS techniques can be optimized to determine the accuracy of organoid models and expand the field of organoid research are also discussed.

Positive feedback drives a secondary nonlinear product burst during a biphasic DNA amplification reaction.

Isothermal DNA amplification reactions are used in a broad variety of applications, from diagnostic assays to DNA circuits, with greater speed and less complexity than established PCR technologies. We recently reported a unique, high gain, biphasic isothermal DNA amplification reaction, called the Ultrasensitive DNA Amplification Reaction (UDAR). Here we present a detailed analysis of the UDAR reaction pathways that initiates with a first phase followed by a nonlinear product burst, which is caused by an autocatalytic secondary reaction. The experimental reaction output was reproduced using an ordinary differential equation model based on detailed reaction mechanisms. This model provides insight on the relative importance of each reaction mechanism during both phases, which could aid in the design of product output during DNA amplification reactions.

Species loss and nitrogen pollution alter litter decomposition dynamics in coastal salt marshes.

Litter decomposition is a central ecosystem function because dead plant biomass plays a critical role in carbon storage, the nitrogen (N) cycle, and as food/habitat for animals and microorganisms. In the face of global change, interactions between organisms that participate in litter decomposition are likely to change due to species loss and N pollution. To understand how these global change factors may interact to alter litter decomposition, we manipulated the detritivore community and N concentrations in a coastal salt marsh for 2 years. We chose to manipulate densities of a dominant, detritivorous snail (Melampus bidentatus) because its population size is expected to decline due to climate change, yet its impact on litter decomposition has not been tested in the field. We measured litter decomposition rates, detritivore densities, and the N concentrations of sediment and litter. We found that endogenous N enrichment (N added live plants before decomposition), exogenous N enrichment (N added to decomposing plants) and higher densities of Melampus increased litter decomposition rates. Linear mixed models further revealed that snails, other detritivores, and soil NH4+ were the best predictors of litter mass loss in the middle stages of decomposition. Notably, exogenous N added to litter already enriched with N further increased mass loss but did not increase litter %N. Our study reveals how global change in the form species loss and N pollution can have palpable impacts on carbon cycling and ecosystem function.

Development of a person-centered interdisciplinary plan-of-care program for dialysis.

BACKGROUND: Dialysis care often focuses on outcomes that are of lesser importance to patients than to clinicians. There is growing international interest in individualizing care based on patient priorities, but evidence-based approaches are lacking. The objective of this study was to develop a person-centered dialysis care planning program. To achieve this objective we performed qualitative interviews, responsively developed a novel care planning program and then assessed program content and burden. METHODS: We conducted 25 concept elicitation interviews with US hemodialysis patients, care partners and care providers, using thematic analysis to analyze transcripts. Interview findings and interdisciplinary stakeholder panel input informed the development of a new care planning program, My Dialysis Plan. We then conducted 19 cognitive debriefing interviews with patients, care partners and care providers to assess the program's content and face validities, comprehensibility and burden. RESULTS: We identified five themes in concept elicitation interviews: feeling boxed in by the system, navigating dual lives, acknowledging an evolving identity, respecting the individual as a whole person and increasing individualization to enhance care. We then developed a person-centered care planning program and supporting materials that underwent 32 stakeholder-informed iterations. Data from subsequent cognitive interviews led to program revisions intended to improve contextualization and understanding, decrease burden and facilitate implementation. CONCLUSIONS: My Dialysis Plan is a content-valid, person-centered dialysis care planning program that aims to promote care individualization. Investigation of the program's capacity to improve patient experiences and outcomes is needed.

Predator population size structure alters consumption of prey from epigeic and grazing food webs.

Numerous studies have found that predators can suppress prey densities and thereby impact important ecosystem processes such as plant productivity and decomposition. However, prey suppression by spiders can be highly variable. Unlike predators that feed on prey within a single energy channel, spiders often consume prey from asynchronous energy channels, such as grazing (live plant) and epigeic (soil surface) channels. Spiders undergo few life cycle changes and thus appear to be ideally suited to link energy channels, but ontogenetic diet shifts in spiders have received little attention. For example, spider use of different food channels may be highly specialized in different life stages and thus a species may be a multichannel omnivore only when we consider all life stages. Using stable isotopes, we investigated whether wolf spider (Pardosa littoralis, henceforth Pardosa) prey consumption is driven by changes in spider size. Small spiders obtained > 80% of their prey from the epigeic channel, whereas larger spiders used grazing and epigeic prey almost equally. Changes in prey consumption were not driven by changes in prey density, but by changes in prey use by different spider size classes. Thus, because the population size structure of Pardosa changes dramatically over the growing season, changes in spider size may have important implications for the strength of trophic cascades. Our research demonstrates that life history can be an important component of predator diet, which may in turn affect community- and ecosystem-level processes.

Geography is more important than host plant use for the population genetic structure of a generalist insect herbivore.

Population divergence can occur due to mechanisms associated with geographic isolation and/or due to selection associated with different ecological niches. Much of the evidence for selection-driven speciation has come from studies of specialist insect herbivores that use different host plant species; however, the influence of host plant use on population divergence of generalist herbivores remains poorly understood. We tested how diet breadth, host plant species and geographic distance influence population divergence of the fall webworm (Hyphantria cunea; FW). FW is a broadly distributed, extreme generalist herbivore consisting of two morphotypes that have been argued to represent two different species: black-headed and red-headed. We characterized the differentiation of FW populations at two geographic scales. We first analysed the influence of host plant and geographic distance on genetic divergence across a broad continental scale for both colour types. We further analysed the influence of host plant, diet breadth and geographic distance on divergence at a finer geographic scale focusing on red-headed FW in Colorado. We found clear genetic and morphological distinction between red- and black-headed FW, and Colorado FW formed a genetic cluster distinct from other locations. Although both geographic distance and host plant use were correlated with genetic distance, geographic distance accounted for up to 3× more variation in genetic distance than did host plant use. As a rare study investigating the genetic structure of a widespread generalist herbivore over a broad geographic range (up to 3,000 km), our study supports a strong role for geographic isolation in divergence in this system.

Prenatal Maternal Stress and the Cascade of Risk to Schizophrenia Spectrum Disorders in Offspring.

PURPOSE OF REVIEW: Disruptions in fetal development (via genetic and environmental pathways) have been consistently associated with risk for schizophrenia in a variety of studies. Although multiple obstetric complications (OCs) have been linked to schizophrenia, this review will discuss emerging evidence supporting the role of prenatal maternal stress (PNMS) in the etiology of schizophrenia spectrum disorders (SSD). In addition, findings linking PNMS to intermediate phenotypes of the disorder, such as OCs and premorbid cognitive, behavioral, and motor deficits, will be reviewed. Maternal immune and endocrine dysregulation will also be explored as potential mechanisms by which PNMS confers risk for SSD. RECENT FINDINGS: PNMS has been linked to offspring SSD; however, findings are mixed due to inconsistent and retrospective assessments of PNMS and lack of specificity about SSD outcomes. PNMS is also associated with various intermediate phenotypes of SSD (e.g., prenatal infection/inflammation, decreased fetal growth, hypoxia-related OCs). Recent studies continue to elucidate the impact of PNMS while considering the moderating roles of fetal sex and stress timing, but it is still unclear which aspects of PNMS (e.g., type, timing) confer risk for SSD specifically. PNMS increases risk for SSD, but only in a small portion of fetuses exposed to PNMS. Fetal sex, genetics, and other environmental factors, as well as additional pre- and postnatal insults, likely contribute to the PNMS-SSD association. Longitudinal birth cohort studies are needed to prospectively illuminate the mechanisms that account for the variability in outcomes following PNMS.

Bottom-up vs. top-down effects on terrestrial insect herbivores: a meta-analysis.

Primary consumers are under strong selection from resource ('bottom-up') and consumer ('top-down') controls, but the relative importance of these selective forces is unknown. We performed a meta-analysis to compare the strength of top-down and bottom-up forces on consumer fitness, considering multiple predictors that can modulate these effects: diet breadth, feeding guild, habitat/environment, type of bottom-up effects, type of top-down effects and how consumer fitness effects are measured. We focused our analyses on the most diverse group of primary consumers, herbivorous insects, and found that in general top-down forces were stronger than bottom-up forces. Notably, chewing, sucking and gall-making herbivores were more affected by top-down than bottom-up forces, top-down forces were stronger than bottom-up in both natural and controlled (cultivated) environments, and parasitoids and predators had equally strong top-down effects on insect herbivores. Future studies should broaden the scope of focal consumers, particularly in understudied terrestrial systems, guilds, taxonomic groups and top-down controls (e.g. pathogens), and test for more complex indirect community interactions. Our results demonstrate the surprising strength of forces exerted by natural enemies on herbivorous insects, and thus the necessity of using a tri-trophic approach when studying insect-plant interactions.

Incidence of Lyme Disease Diagnosis in a Maryland Medicaid Population, 2004-2011.

The epidemiology of Lyme disease has been examined utilizing insurance claims from privately insured individuals; however, it is unknown whether reported patterns vary among the publicly insured. We examined trends in incidence rates of first Lyme disease diagnosis among 384,652 Maryland Medicaid recipients enrolled from July 2004 to June 2011. Age-, sex-, county-, season-, and year-specific incidence rates were calculated, and mixed-effects multiple logistic regression models were used to study the relationship between Lyme disease diagnosis and these variables. The incidence rate in our sample was 97.65 cases per 100,000 person-years (95% confidence interval (CI): 91.53, 104.06), and there was a 13% average annual increase in the odds of a Lyme disease diagnosis (odds ratio = 1.13, 95% CI: 1.09, 1.17; P < 0.001). Incidence rates for males and females were not significantly different, though males were significantly more likely to be diagnosed during high-season months (relative risk (RR) = 1.24, 95% CI: 1.06, 1.44) and less likely to be diagnosed during low-season months (RR = 0.63, 95% CI: 0.46, 0.87) than females. Additionally, adults were significantly more likely than children to be diagnosed during low-season months (RR = 1.59, 95% CI: 1.19, 2.12). While relatively rare in this study sample, Lyme disease diagnoses do occur in a Medicaid population in a Lyme-endemic state.

Genetic Determinants of Penicillin Tolerance in Vibrio cholerae.

Many bacteria are resistant to killing (tolerant) by typically bactericidal antibiotics due to their ability to counteract drug-induced cell damage. Vibrio cholerae, the cholera agent, displays an unusually high tolerance to diverse inhibitors of cell wall synthesis. Exposure to these agents, which in other bacteria leads to lysis and death, results in a breakdown of the cell wall and subsequent sphere formation in V. cholerae Spheres readily recover to rod-shaped cells upon antibiotic removal, but the mechanisms mediating the recovery process are not well characterized. Here, we found that the mechanisms of recovery are dependent on environmental conditions. Interestingly, on agarose pads, spheres undergo characteristic stages during the restoration of rod shape. Drug inhibition and microscopy experiments suggest that class A penicillin binding proteins (aPBPs) play a more active role than the Rod system, especially early in sphere recovery. Transposon insertion sequencing (TnSeq) analyses revealed that lipopolysaccharide (LPS) and cell wall biogenesis genes, as well as the sigma E cell envelope stress response, were particularly critical for recovery. LPS core and O-antigen appear to be more critical for sphere formation/integrity and viability than lipid A modifications. Overall, our findings demonstrate that the outer membrane is a key contributor to beta lactam tolerance and suggest a role for aPBPs in cell wall biogenesis in the absence of rod-shape cues. Factors required for postantibiotic recovery could serve as targets for antibiotic adjuvants that enhance the efficacy of antibiotics that inhibit cell wall biogenesis.

Quantitative measure of fitness in tri-trophic interactions and its influence on diet breadth of insect herbivores.

Herbivore-plant interactions should be studied using a tri-trophic approach, but we lack a quantitative measure of the combined effect of top-down and bottom-up forces on herbivore fitness. We propose the combination of the bi-trophic fitness slopes as a tri-trophic fitness measure. We use the relationship between fitness associated with top-down and bottom-up forces and the frequency of host plant use to calculate the top-down and bottom-up fitness slopes, which we then combine to obtain three possible directions of tri-trophic slopes. A positive tri-trophic slope indicates that herbivores have overall greater tri-trophic fitness on the more frequently used hosts. A null tri-trophic fitness slope indicates that herbivores have similar fitness on all host plants. A negative tri-trophic slope indicates that herbivores have generally lower fitness on the more frequently used hosts. We tested the explanation power of our method using data from the literature that tested herbivore host shifts and experimentally using a generalist herbivore with variable diet breadth across populations. We found that in host shifts, herbivores have higher tri-trophic fitness on the novel host, while in generalist populations, herbivores use most frequently the best host available. We present applications in other research areas and consider the limitations of our approach. Our approach is a first step towards a comprehensive model of multiple selective forces acting on the evolution of interactions.

Going Beyond Clinical Care to Reduce Health Care Spending: Findings From the J-CHiP Community-based Population Health Management Program Evaluation.

BACKGROUND: Addressing both clinical and nonclinical determinants of health is essential for improving population health outcomes. In 2012, the Johns Hopkins Community Health Partnership (J-CHiP) implemented innovative population health management programs across acute and community environments. The community-based program involved multidisciplinary teams [ie, physicians, care managers (CM), health behavior specialists (HBS), community health workers, neighborhood navigators] and collaboration with community-based organizations to address social determinants. OBJECTIVES: To report the impact of a community-based program on cost and utilization from 2011 to 2016. DESIGN: Difference-in-difference estimates were calculated for an inclusive cohort of J-CHiP participants and matched nonparticipants. The analysis was replicated for participants with a CM and/or HBS to estimate the differential impact with more intensive program services. SUBJECTS: A total of 3268 high-risk Medicaid and Medicare beneficiaries (1634 total J-CHiP participants, 1365 with CM and 678 with HBS). OUTCOME MEASURES: Paid costs and counts of emergency department visits, admissions, and readmissions per member per year. RESULTS: For Medicaid, costs were almost $1200 per member per year lower for participants as a whole, $2000 lower for those with an HBS, and $3000 lower for those with a CM; hospital admission and readmission rates were 9%-26% lower for those with a CM and/or HBS. For Medicare, costs were lower (-$476), but utilization was similar or higher than nonparticipants. None of the observed Medicaid or Medicare differences were statistically significant. CONCLUSIONS: Although not statistically significant, the results indicate a promising innovation for Medicaid beneficiaries. For Medicare, the impact was negligible, indicating the need for further program modification.

Time-lagged intraspecific competition in temporally separated cohorts of a generalist insect.

Competition can have far-reaching consequences for insect fitness and dispersion. Time-lagged interspecific competition is known to negatively affect fitness, yet time-lagged intraspecific competition is rarely studied outside of outbreak conditions. We tested the impact of competition between larval cohorts of the western tent caterpillar (Malacosoma californicum) feeding on chokecherry (Prunus virginiana). We reared larvae on host plants that either had or did not have feeding damage from tent caterpillars the previous season to test the bottom-up fitness effects of intraspecific competition. We measured host-plant quality to test potential mechanisms for bottom-up effects and conducted field oviposition surveys to determine if female adult tent caterpillars avoided host plants with evidence of prior tent caterpillar presence. We found that time-lagged intraspecific competition impacted tent caterpillar fitness by reducing female pupal mass, which is a predictor of lifetime fitness. We found that plants that had been fed upon by tent caterpillars the previous season had leaves that were significantly tougher than plants that had not been fed upon by tent caterpillars, which may explain why female tent caterpillars suffered reduced fitness on these plants. Finally, we found that there were fewer tent caterpillar egg masses on plants that had tent caterpillars earlier in the season than plants without tent caterpillars, which suggests that adult females avoid these plants for oviposition. Our results confirm that intraspecific competition occurs among tent caterpillars and suggests that time-lagged intraspecific competition has been overlooked as an important component of insect fitness.

Trade-offs in host choice of an herbivorous insect based on parasitism and larval performance.

Herbivore diet breadth is predicted to evolve in response to both bottom-up and top-down selective pressures, including host plant abundance, quality and natural enemy pressure. As the relative importance and strength of interactions change over an herbivore's geographic range, local patterns of host plant use should change in response, altering local diet breadths. Fall webworm (Hyphantria cunea) is a widespread, polyphagous moth species that feeds on hundreds of plant species worldwide. Populations of fall webworm in Colorado remain polyphagous, but their diet breadth is restricted compared to other populations and thus present an ideal opportunity to test the ecological drivers of host use by a polyphagous herbivore. We investigated how host abundance, larval performance, and parasitism affect host use for fall webworm to test how these selective pressures may act individually or in concert, as well as the role of any trade-offs among fitness components, to explain diet breadth and host use. We found that host abundance was a significant predictor of host use, which suggests a selective pressure to reduce search time for oviposition sites by adult females. We also detected an important trade-off between bottom-up and top-down selective pressures: higher quality host plants also had a greater proportion of larval mortality due to parasitism. Local patterns of host plant abundance appear to narrow the set of hosts used by fall webworms in Colorado, while the trade-off between host quality and risk of parasitism helps explain the maintenance of a generalized feeding strategy within this restricted set of hosts.