Biology subjects

Moran, D.

Publications and source records attributed to Moran, D..

8 recordsLinked to original sources

bioRxiv2025

A socio-ecological System Dynamics model of antimicrobial use and resistance

The concept of resource extraction in the context of antimicrobial resistance (AMR) is rarely explored. In this framework, antimicrobial susceptibility is viewed as a finite resource that is depleted through the use of antimicrobials --thus, AMR represents the exhaustion of this resource. In this work, we examine the system dynamics of AMR using causal loop diagrams to define both the structure and behaviour of two variants of the system. We then evaluate the robustness of the system dynamics models through sensitivity testing. The first model is inspired by a classic "Limits to Growth" structure, in which antimicrobial use practices depend on recent observations of treatment success or failure. The second differs by including AMR surveillance informing antimicrobial prescribing instead of anecdotal experience. The models consider one "bug-drug-mutation-context" combination at a time, but can be applied to different microbes, antimicrobials, and host populations in human or veterinary contexts. Multiparameter sensitivity analyses of relative fitness and timescale parameters were carried out on both model variants. Several key differences in model behaviour over time were observed between the socio-ecological Limits to Growth structure and the modified version in which human judgment, with its associated time lag, is bypassed. The models help explore the effects of human behaviour and associated time lags on patterns of population-level antimicrobial susceptibility over time, applying an established modelling technique in a novel context to generate new insights - notably that plateaux in AMR observed in the field could be in part due to human behaviour rather than purely evolutionary forces. The framing of antimicrobial susceptibility as a variably renewable natural resource is valuable not only as an avenue for alternative modelling approaches, but also as a more collaborative framing for public and policy engagement to promote sustainable management of this common pool resource.

microbiology↗

bioRxiv2025

Selective breeding and production strategies to support snapper farming in the warming waters of New Zealand's South Island

Diversifying aquaculture species is essential for building resilience in the face of climate change, particularly as warming oceans challenge existing production systems. In New Zealands Marlborough Sounds, rising sea temperatures are making salmon farming increasingly difficult, highlighting the need for climate-adapted alternatives. This study evaluated the aquaculture performance of selectively bred F4 versus unselected F1 Australasian snapper (Chrysophrys auratus) across two rearing environments: sea pens in the Marlborough Sounds and a land-based system in Nelson. Approximately 1,000 F4 and 1,000 F1 snapper were reared from 4 to 30 months of age in each system. At 30 months, selectively bred snapper showed improved growth-body length increased by 1.7% (land-based) and 4.8% (ocean-based), and body weight by 9.8% and 14.2%, respectively compared with F1 snapper. Survival was also significantly higher, with selected snapper outperforming controls by 84.2% in the land-based and 60.8% in the ocean-based system. Mortality peaked in the first winter across both systems, with size-selective patterns in sea pens informing minimum stocking sizes. These findings offer important insights for refining husbandry and selective breeding practices. They are not only relevant for New Zealand but also for global aquaculture sectors seeking robust species suited to changing marine environments.

zoology↗

bioRxiv2024

Fecal Metabolite Quantitation for Rapid Assessment of the Gut Microbiome

The intestinal microbiome is composed of myriad microbial species that produce metabolites that impact host health. While loss of bacterial species and beneficial metabolites from the fecal microbiome is associated with development of a range of diseases and medical complications, there are currently no diagnostic tests that rapidly identify individuals with microbiome deficiencies. Reduced concentrations of fecal butyrate and deoxycholic acid are associated with adverse clinical outcomes and result from the loss of a subset of health-associated bacterial species. We present a rapid diagnostic test based on 3-nitrophenylhydrazine derivatization and ultrahigh-performance liquid chromatography-mass spectrometry that measures fecal butyrate and deoxycholic acid concentrations as markers of microbiome function. A matrix-matched calibration curve was developed using a simulated fecal mixture to optimize accuracy and facilitate adherence to clinical laboratory regulations. The assay showed an analytical measurement range from 4.3-3030.1 {micro}M (LLOQ = 9.75 {micro}M) for butyrate and from 0.9- 64.9 {micro}M (LLOQ = 0.9 {micro}M) for deoxycholic acid. Precision demonstrated a coefficient of variation <15% at all QC levels tested. The assay can be performed in under an hour from extraction to provision of quantitative results, enabling the rapid identification of patients with defective microbiome function.

pathology↗

bioRxiv2024

Protection against Clostridioides difficile disease by a naturally avirulent C. difficile strain

Clostridioides difficile (C. difficile) strains belonging to the epidemic BI/NAP1/027 (RT027) group have been associated with increased transmissibility and disease severity. In addition to the major toxin A and toxin B virulence factors, RT027 strains also encode the CDT binary toxin. Our lab previously identified a toxigenic RT027 isolate, ST1-75, that is avirulent in mice despite densely colonizing the colon. Here, we show that co-infecting mice with the avirulent ST1-75 and virulent R20291 strains protects mice from colitis due to rapid clearance of the virulent strain and persistence of the avirulent strain. Although avirulence of ST1-75 is due to a mutation in the cdtR gene, which encodes a response regulator that modulates the production of all three C. difficile toxins, the ability of ST1-75 to protect against acute colitis is not directly attributable to the cdtR mutation. Metabolomic analyses indicate that the ST1-75 strain depletes amino acids more rapidly than the R20291 strain and supplementation with amino acids ablates ST1-75s competitive advantage, suggesting that the ST1-75 strain limits the growth of virulent R20291 bacteria by amino acid depletion. Since the germination kinetics and sensitivity to the co-germinant glycine are similar for the ST1-75 and R20291 strains, our results identify the rapidity of in vivo nutrient depletion as a mechanism providing strain-specific, virulence-independent competitive advantages to different BI/NAP1/027 strains. They also suggest that the ST1-75 strain may, as a biotherapeutic agent, enhance resistance to CDI in high-risk patients. ImportanceClostridioides difficile infections (CDI) are prevalent in healthcare settings and are associated with high recurrence rates. Therapies to prevent CDI, including recent FDA-approved live biotherapeutic products, are costly and have not been used to prevent primary infections. While a nontoxigenic C. difficile strain (NTCD-M3) protects against virulent CDI in animals and reduced CDI recurrence in a phase 2 clinical trial, protection against CDI recurrence in humans was variable and required high doses of the nontoxigenic strain. Here we show that an avirulent C. difficile isolate, ST1-75, efficiently outcompetes virulent C. difficile strains in mice when co-infected at a 1:1 ratio. Our data suggest that inter-strain competition results from ST1-75s more rapid depletion of amino acids than the virulent R20291 strain. Our study identifies inter-strain nutrient depletion as a potentially exploitable mechanism to reduce the incidence of CDI.

microbiology↗

bioRxiv2024

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species and strain level diversity and evolution

Species of the Bacteroidales order are among the most abundant and stable bacterial members of the human gut microbiome with diverse impacts on human health. While Bacteroidales strains and species are genomically and functionally diverse, order-wide comparative analyses are lacking. We cultured and sequenced the genomes of 408 Bacteroidales isolates from healthy human donors representing nine genera and 35 species and performed comparative genomic, gene-specific, mobile gene, and metabolomic analyses. Families, genera, and species could be grouped based on many distinctive features. However, we also show extensive DNA transfer between diverse families, allowing for shared traits and strain evolution. Inter- and intra-specific diversity is also apparent in the metabolomic profiling studies. This highly characterized and diverse Bacteroidales culture collection with strain-resolved genomic and metabolomic analyses can serve as a resource to facilitate informed selection of strains for microbiome reconstitution.

microbiology↗

bioRxiv2022

Exceptionally versatile respiratory metabolisms drive metabolite production by diverse gut bacteria

Respiratory reductases enable microbes to utilize molecules present in anaerobic ecosystems as energy-generating respiratory electron acceptors. Here we identify three taxonomically distinct families of human gut bacteria (Burkholderiaceae, Eggerthellaceae, Erysipelotrichaceae) that encode large arsenals of tens-to-hundreds of respiratory-like reductases per genome. Screening species from each family (Sutterella wadsworthensis, Eggerthella lenta, and Holdemania filiformis), we discover 22 metabolites used as respiratory electron acceptors in a species-specific manner. Identified reactions transform multiple classes of dietary- and host-derived metabolites, including bioactive molecules resveratrol and itaconate. Products of identified respiratory metabolisms highlight poorly characterized compounds, such as the itaconate-derived 2-methylsuccinate. Reductase substrate-profiling defines enzyme-substrate pairs and reveals a complex picture of reductase evolution, providing evidence that reductases with specificities for related cinnamate substrates independently emerged at least four times. These studies thus establish an exceptionally versatile form of anaerobic respiration that directly links microbial energy metabolism to the gut metabolome.

microbiology↗

bioRxiv2022

Independent evolution of influenza A virus H1N1 in pigs in Guatemala

Commercial swine farms provide unique systems for interspecies transmission of influenza A viruses (FLUAVs) at the animal-human interface. Bidirectional transmission of FLUAVs between pigs and humans plays a significant role in the generation of novel strains that become established in the new host population. Active FLUAV surveillance was conducted for two years on a commercial pig farm in Southern Guatemala with no history of FLUAV vaccination. Nasal swabs (n=2,094) from fattening pigs (6 to 24 weeks old) with respiratory signs were collected from May 2016 to February 2018. Swabs were screened for FLUAV by RRT-PCR and full virus genomes of FLUAV-positive swabs were sequenced by next-generation sequencing (NGS). FLUAV prevalence was 12.0% (95% CI: 10.6% - 13.4%) with two distinct periods of high infection. All samples were identified as FLUAVs of the H1N1 subtype within the H1 swine clade 1A.3.3.2 and whose ancestors are the human origin 2009 H1N1 influenza pandemic virus (H1N1 pdm09). Compared to the prototypic reference segment sequence, 10 amino acid signatures were observed on relevant antigenic sites on the hemagglutinin. We also found that Guatemalan swine-origin FLUAVs show independent evolution from other H1N1 pdm09 FLUAVs circulating in Central America. The zoonotic risk of these viruses remains unknown, but strongly calls for continued FLUAV surveillance in pigs in Guatemala. ImportanceDespite increased surveillance efforts, the epidemiology of FLUAVs circulating in swine in Latin America remains understudied. For instance, the 2009 H1N1 influenza pandemic strain (H1N1 pdm09) emerged in Mexico, but its circulation remained undetected in pigs. In Central America, Guatemala is the country with the largest swine industry. We found a unique group of H1N1 pdm09 sequences that suggests independent evolution from similar viruses circulating in Central America. These viruses may represent the establishment of a novel genetic lineage with the potential to reassort with other co-circulating viruses, and whose zoonotic risk remains to be determined.

evolutionary biology↗

bioRxiv2017

Promoter-Enhancer Interactions Identified from Hi-C Data using Probabilistic Models and Hierarchical Topological Domains

Proximity-ligation methods as Hi-C allow us to map physical DNA-DNA interactions along the genome, and reveal its organization in topologically associating domains (TADs). As Hi-C data accumulate, computational methods were developed for identifying domain borders in multiple cell types and organisms.\n\nHere, we present PSYCHIC, a computational approach for analyzing Hi-C data and identifying Promoter-Enhancer interactions. We use a unified probabilistic model to segment the genome into domains, which we merge hierarchically and fit the Hi-C interaction map with a local background model. This allows us to estimate the expected number of interactions for every DNA-DNA pair, thus identifying over-represented interactions across the genome.\n\nBy analyzing published Hi-C data in human and mouse, we identified hundreds of thousands of putative enhancers and their target genes in multiple cell types, and compiled an extensive genome-wide catalog of gene regulation in human and mouse.

bioinformatics↗