Biology subjects

Smith, A. M.

Publications and source records attributed to Smith, A. M..

At least 19 recordsLinked to original sources

bioRxiv2026

Night-time control of carbohydrate availability in grasses differs radically from that in Arabidopsis

Grass leaves reportedly accumulate sucrose during the day then export it to other organs at night. The control of export at night is not understood. In contrast, Arabidopsis leaves accumulate starch then convert it to sucrose for export at night. Control of starch mobilisation ensures a constant sucrose supply and exhaustion of starch around anticipated dawn. We found that that 41 species of pooid grasses differed widely in the ratio of sucrose to starch accumulation and night-time depletion (turnover) in leaf blades, regardless of growth conditions. Sucrose turnover exceeded starch turnover in most species, but in a minority of species the two were similar. In eight species spanning this diversity, the rate of sucrose depletion fell through the night. In six of the species, all with higher sucrose than starch turnover, starch depletion at night was initially slow. Later, it increased to a rate that exhausted starch around dawn. The initial lag was absent and starch depletion was linear throughout the night in the other two species, both of which had similar sucrose and starch turnover. We suggest that underlying control of starch mobilisation in grass leaf blades resembles that in Arabidopsis leaves. The initial lag in starch depletion in high-sucrose species may result from suppression of starch degradation by sucrose, acting via the sucrose signalling metabolite Tre6P. The large diel fluctuations in sucrose export from grass leaf blades may be dampened by exchange with dynamic pools of sucrose in leaf bases and sheaths prior to export to other organs.

plant biology↗

bioRxiv2026

Advancing Great Lakes Coastal Wetland Food Web Models Using an Integrative Tracer Approach

Coastal wetlands of the Laurentian Great Lakes support abundant populations of fish, invertebrates, and vegetation, though the trophic linkages connecting primary production and lower consumers is not well understood in these systems. We implemented a multiple-tracer approach to evaluate trophic pathways, pairing traditional food web isotope tracers like carbon ({delta}13C) and nitrogen ({delta}15N) with total mercury concentrations (THg). We predicted that filamentous algae would be the dominant energy resource in the diet of lower trophic-level invertebrates in the Grand River Estuary, a network of riverine coastal wetlands adjacent to Lake Michigan. In addition, we predicted that adding THg as a tracer would improve the resolution of our food web models by clarifying trophic levels and relationships between wetland species. Four basal energy sources were sampled, including filamentous algae, emergent macrophytes, submersed macrophytes, and phytoplankton, along with organic detritus. Aquatic invertebrates were sampled across multiple functional guilds to represent primary and secondary consumers and included amphipods and odonates. Our findings suggest that organic detritus is the dominant resource responsible for energetically supporting these lower trophic levels in the Grand River estuary, although submersed macrophytes were important alternative energy sources for secondary consumers. THg concentrations enhanced the resolution of dietary contribution estimates in MixSIAR models applied to consumer and source data. Isotope biplots revealed that THg concentrations were a more reliable predictor of trophic position than {delta}15N in Grand River Estuary (GRE) sites. This methodology has important implications for future food web studies in complex ecosystems such as coastal wetlands and demonstrates the novel use of mercury as an ecological tracer in a Bayesian mixing model approach.

ecology↗

bioRxiv2026

Evolution of multidrug-resistant IncC plasmids in the seventh pandemic Vibrio cholerae O1 El Tor lineage between 1979 and 2024

IncC plasmids played an important role in driving antimicrobial drug resistance development in the seventh pandemic Vibrio cholerae O1 El Tor (7PET) lineage during the 1970s and these have begun to re-emerge. In this study, we investigated a comprehensive dataset for 28 complete IncC plasmids -- including 17 newly sequenced plasmid genomes -- from 7PET isolates collected on various continents between 1979 and 2024 and distributed across the global phylogenetic tree for 7PET isolates. IncC type 2 predominated among the V. cholerae plasmids studied, and five new core genome sequence types (cgSTs) were identified. The antimicrobial resistance genes (ARGs) were arranged in islands inserted at specific hotspots within the common IncC backbone and were significantly associated with IncC types or islands. The IncC plasmid backbone has remained stable over the last 50 years, but the ARGs and their associated genomic islands displayed remarkable diversity, underscoring the complex evolution patterns of the 7PET lineage of V. cholerae and its considerable adaptability under selective pressure.

microbiology↗

bioRxiv2026

Adenocarcinoma cell mechanobiology is altered by the loss modulus of the surrounding extracellular matrix

Elastic and viscoelastic properties of extracellular matrices (ECM) are known to regulate cellular behavior and mechanosensation differently, with implications for morphogenesis, wound healing, and pathophysiology. Most in vitro cellular processes, including cell migration, are studied on linear-elastic substrates to mimic extracellular matrices. However, most tissues are viscoelastic and display a loss modulus (G) that may be 10-20% of their storage modulus (G) under biophysically relevant conditions. Recent research has shown that cells can distinguish between elastic and viscoelastic ECM, leading to alterations in their cellular morphology, migration rates, and contractility. Here, we present a protocol for creating PAH-based model ECMs that enables the fabrication of viscoelastic substrates with storage moduli similar to those of their elastic counterparts. To explore how G influences epithelial cell mechanobiology, we fabricated tunable viscoelastic model ECMs with G of 3 kPa, 8 kPa, and 12 kPa, and for each, independently tuned G values to approximately 300 Pa, 500 Pa, and 700 Pa, respectively. We found that A549 cells cultured on stiff elastic model ECMs migrated [~]30% slower and formed larger focal adhesions compared to their viscoelastic counterparts. Conversely, A549 cells on intermediate viscoelastic model ECMs exhibited a [~]54% reduction in migration speed, with no significant difference in focal adhesion size relative to their elastic counterparts. These findings highlight the complex interplay between substrate (ECM) elastic and viscoelastic properties in regulating epithelial cell mechanobiology and emphasize the importance of time-dependent matrix mechanics in governing epithelial responses.

biophysics↗

bioRxiv2026

Changes in microhabitat structure around amphibian breeding ponds in the northern Rocky Mountains following severe wildfire

Microhabitats promote diverse and resilient forests. Wildfire may alter critical microhabitat, yet studies directly quantifying these effects are limited. Here, we use a rare before-after-control-impact dataset to assess the impacts of severe wildfire on fine-scale gradients in microhabitat structure associated with amphibian breeding ponds in the Rocky Mountains. Using 462 photoquadrats sampled eight years before and two years after the 2017 Kenow wildfire in Waterton Lakes National Park, we quantified changes in 14 microhabitat features at three different distances (0, 3, and 10 m) away from burned and unburned ponds. Non-parametric multivariate analysis of variance suggested distance from pond edge was a significant predictor of microhabitat composition prior to the wildfire, with the proportion of soil (bare ground) decreasing and the proportion of shrubs and forbs increasing away from pond edges. A significant interaction between distance, burn status, and time was observed, suggesting that the relationship between microhabitat and distance depended on the joint effects of burn status and time. This result was driven by changes 10 m away from pond edges in the burn zone, where sites experienced an increase in the proportion of forbs, soil, gravel, and rocks, and the loss of moss cover following the fire. Microhabitat change was more pronounced at high elevation sites, although power to statistically test the effect of elevation was limited. Our study demonstrates heterogeneity in the impacts of wildfire on microhabitats along fine-scale gradients. We discuss implications of these findings for the management of amphibians using these sites.

ecology↗

bioRxiv2025

BLASE: Bulk Linkage Analysis for Single Cell Experiments - Teasing Out the Secrets of Bulk Transcriptomics with Trajectory Analysis

1MotivationscRNA-seq experiments can capture cell process trajectories. Bulk RNA-seq is more practical, however does not have the granularity to elucidate cell-type specific trajectories. Deconvolution methods can estimate cell-types in RNA-seq data, but there is a need for methods characterising their pseudotime. ResultsWe show that our method, BLASE, can identify the progress of an RNA-seq sample through a trajectory in a scRNA-seq reference. ConclusionBLASE can be used to a) annotate scRNA-seq data from existing RNA-seq, b) identify progress of RNA-seq data through a process based on scRNA-seq data, and c) be used to correct developmental differences in RNA-seq differential expression analysis.

bioinformatics↗

bioRxiv2025

Repeated extrinsic rewards following retrieval practice facilitate later memory

The anticipation of extrinsic reward facilitates memory formation. However, it is unclear how reward following memory retrieval influences the information that is retrieved and later remembered. Here, we conducted four behavioral experiments (N=42 male/female young adults per experiment) in which we manipulated retrieval practice reward delivery. Across all experiments, participants studied word-image pairs and then completed two rounds of retrieval practice, followed by a final recognition test. Participants made vividness judgments during retrieval practice and in three of four experiments each response had a 50% chance of yielding positive feedback. We find that repeated rewards following retrieval practice facilitate later memory whereas low vivid retrieval practice impairs later memory. Together, these results suggest that the benefit of both retrieval practice and reward may be dependent on the strength of the memory that is retrieved.

neuroscience↗

bioRxiv2025

TOWARDS CLIMATE-SMART REWILDING: AN INTEGRATED FRAMEWORK FOR BIODIVERSITY, CLIMATE CHANGE, AND SOCIETY

The UN Decade on Ecosystem Restoration and the Kunming-Montreal Global Biodiversity Framework aim to restore 30% of degraded ecosystems. Both the IPCC and IPBES highlight the crucial role of ecosystem restoration in addressing the interconnected crises of climate change and biodiversity loss. One key restoration strategy is rewilding, which enhances ecosystem complexity with minimal human intervention. While traditional rewilding strategies often focus on benefits for biodiversity, we propose a climate-smart rewilding framework as a new approach designed to deliver climate benefits alongside biodiversity restoration. This framework seeks to integrate biodiversity, climate change adaptation and mitigation, as well as socio-economic benefits and trade-offs. We illustrate how this framework can be utilized to identify areas across Europe where rewilding could increase carbon sequestration, enhance species abilities to adapt to the velocity of climate change, and maximize wildlife-watching benefits while minimizing the costs associated with livestock-wildlife conflict. Finally, we acknowledge some limitations of climate-smart rewilding, but we argue that its adaptability and low cost render it a promising solution to the challenges facing Europe and beyond.

ecology↗

bioRxiv2024

Lipid Nanoparticle Barcoding for Multiplexed Single-Cell RNA Sequencing

Sample multiplexing is an emerging method in single-cell RNA sequencing (scRNA-seq) that addresses high costs and batch effects. Current multiplexing schemes use DNA labels to barcode cell samples but are limited in their stability and extent of labeling across heterogeneous cell populations. Here, we introduce Nanocoding using lipid nanoparticles (LNPs) for high barcode labeling density in multiplexed scRNA-seq. LNPs reduce dependencies on cell surface labeling mechanisms due to multiple controllable means of cell uptake, amplifying barcode loading 10-100-fold and allowing both protection and efficient release by dissolution. In cultured cell lines and heterogeneous cells from tissue digests, Nanocoding occurs in 40 minutes with stability after sample mixing and requires only commercially available reagents without novel chemical modifications. In spleen digests, 6-plex barcoded samples show minimal unlabeled cells, with all barcodes giving bimodal count distributions. Challenging samples containing lipid-rich debris and heterogeneous cells from adipose tissue of obese rodents show more than 95% labeling with all known subtypes identified. Using Nanocoding, we investigate gene expression changes related to aging in adipose tissue, profiling cells that could not be readily identified with current direct conjugate methods using lipid or antibody conjugates. This ease of generating and tuning these constructs may afford efficient and robust whole-sample multiplexing with minimal sample crosstalk.

bioengineering↗

bioRxiv2024

Toxicity and Biodegradation of Two Different Hydrothermal Liquefaction Process Waters to Anaerobic Digestion and the Effect of Microaeration

Hydrothermal liquefaction (HTL) can convert a considerable portion of the carbon in complex feedstocks into renewable bio-oil, but it also generates a liquid byproduct (i.e., HTL process water) that retains 15 - 55% of the carbon from the HTL feedstock. Feeding HTL process water to anaerobic digestion (AD) is a promising approach for maximizing resource recovery, enabling the conversion of the retained carbon into biogas. However, various toxic and poorly biodegradable compounds in HTL process water make its treatment with AD challenging. Presently, the underlying mechanisms remain often unclear. We investigated the impact of HTL process water from two different feedstocks - a food-waste proxy (i.e., dog food, rich in proteins) and wheat straw (rich in lignocellulose) - on the different trophic groups in the food web of AD. We found that methanogens rather than acidogens were inhibited by HTL process water. Comparative toxicity and biodegradability analyses showed that wheat-straw process water had a higher biodegradability regardless of its higher toxicity to acetoclastic methanogens than food-waste process water, due to its higher content in toxic but easily degradable aromatic compounds. Microaeration enhanced the biodegradation and methane yields of food-waste process water, particularly under anoxic conditions. However, microaeration was ineffective for wheat-straw process water. These findings highlight the importance of feedstock-specific strategies to optimize AD for biogas production from HTL process water.

bioengineering↗

bioRxiv2024

Typhi Mykrobe: fast and accurate lineage identification and antimicrobial resistance genotyping directly from sequence reads for the typhoid fever agent Salmonella Typhi

BackgroundTyphoid fever results from systemic infection with Salmonella enterica serovar Typhi (Typhi) and causes 10 million illnesses annually. Disease control relies on prevention (water, sanitation, and hygiene interventions or vaccination) and effective antimicrobial treatment. Antimicrobial resistant (AMR) Typhi lineages have emerged and become established in many parts of the world. Knowledge of local pathogen populations informed by genomic surveillance, including of lineages (defined by the GenoTyphi scheme) and AMR determinants, is increasingly used to inform local treatment guidelines and to inform vaccination strategy. Current tools for genotyping Typhi require multiple read alignment or assembly steps and have not been validated for analysis of data generated with Oxford Nanopore Technologies (ONT) long-read sequencing devices. Here, we introduce Typhi Mykrobe, a command line software tool for rapid genotyping of Typhi lineages, AMR determinants, and plasmid replicons direct from sequencing reads. ResultsWe validated Typhi Mykrobe lineage genotyping by comparison with the current standard read mapping-based approach and demonstrated 99.8% concordance across nearly 13,000 genomes sequenced with Illumina platforms. For the few isolates with discordant calls, we show that Typhi Mykrobe results are better supported by the evidence from raw sequence read data than the results generated using the mapping-based approach. We also demonstrate 99.9% concordance for detection of AMR determinants compared with the current standard assembly-based approach, with similar results for plasmid marker detection. Typhi Mykrobe predicts clinical resistance categorisation (S/I/R) for eight drug classes, and we show strong agreement with phenotypic categorisations generated from reference laboratory minimum inhibitory concentration (MIC) data for n=1,572 Illumina-sequenced isolates (>99% agreement within one doubling dilution). We show strong concordance (>96% for genotype and >98% for AMR and plasmid) between calls made from ONT reads and those made from Illumina reads for isolates sequenced on both platforms (n =93 genomes). Typhi Mykrobe takes less than a minute per sample and is available at https://github.com/typhoidgenomics/genotyphi. ConclusionsTyphi Mykrobe provides rapid and sensitive genotyping of Typhi genomes direct from Illumina and ONT reads, although lower accuracy was observed for R9 ONT data. It demonstrated accurate assignment of GenoTyphi lineage, detection of AMR determinants and prediction of corresponding AMR phenotypes, and identification of plasmid replicons.

microbiology↗

bioRxiv2024

The HIV-1 Nuclear Export Complex Reveals the Role of RNA in Crm1 Cargo Recognition

Crm1 is a highly conserved nuclear exportin that transports >1000 human proteins including ribonucleoprotein (RNP) complexes. The interface between Crm1 and RNP cargos is unknown. The HIV regulatory protein, Rev, was one of the first identified cargos for Crm1 and contains a prototypic nuclear export sequence (NES). We present the cryo-electron microscopy structure of the HIV-1 nuclear export complex (Crm1/Ran-GTP and the Rev/RRE RNP). Rev binds at a previously unseen protein-protein binding site that stabilizes a unique Crm1 dimer and positions two NESs within the Crm1 dimer. The orientation of Rev binding positions the RRE within a charged pocket on the inside of the Crm1 toroid, mediating direct RNA-Ran-GTP contacts, highlighting the significant role of the RRE in the interaction. Structure based mutations, combined with cell-based assays, show that Crm1 has multiple distinct cargo recognition sites and explains how Crm1 can recognize a diverse range of protein and RNP cargos.

biochemistry↗

bioRxiv2024

Using virtual patient cohorts to uncover immune response differences in cancer and immunosuppressed COVID-19 patients

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in millions of deaths globally. Adults with immunosuppression (e.g., solid organ transplant recipients) and those undergoing active cancer treatments experience worse infections and more severe COVID-19. It is difficult to conduct clinical studies in these populations, resulting in a restricted amount of data that can be used to relate mechanisms of immune dysfunction to COVID-19 outcomes in these vulnerable groups. To study immune dynamics after infection with SARS-CoV-2 and to investigate drivers of COVID-19 severity in individuals with cancer and immunosuppression, we adapted our mathematical model of the immune response during COVID-19 and generated virtual patient cohorts of cancer and immunosuppressed patients. The cohorts of plausible patients recapitulated available longitudinal clinical data collected from patients in Montreal, Canada area hospitals. Our model predicted that both cancer and immunosuppressed virtual patients with severe COVID-19 had decreased CD8+ T cells, elevated interleukin-6 concentrations, and delayed type I interferon peaks compared to those with mild COVID-19 outcomes. Additionally, our results suggest that cancer patients experience higher viral loads (however, with no direct relation with severity), likely because of decreased initial neutrophil counts (i.e., neutropenia), a frequent toxic side effect of anti-cancer therapy. Furthermore, severe cancer and immunosuppressed virtual patients suffered a high degree of tissue damage associated with elevated neutrophils. Lastly, parameter values associated with monocyte recruitment by infected cells were found to be elevated in severe cancer and immunosuppressed patients with respect to the COVID-19 reference group. Together, our study highlights that dysfunction in type I interferon and CD8+ T cells are key drivers of immune dysregulation in COVID-19, particularly in cancer patients and immunosuppressed individuals.

immunology↗

bioRxiv2023

Altered astrocytic and microglial homeostasis characterizes a decreased proinflammatory state in bipolar disorder

Multiple lines of evidence point to peripheral immune alterations in bipolar disorder (BD) although the activity of brain immune mechanisms remain largely unexplored. To identify the cell type-specific immune alterations in the BD brain, we performed a proteomic and single nuclear transcriptomic analysis of postmortem cingulate cortex samples from BD and control subjects. Our results showed that genes associated to the genetic risk for BD are enriched in microglia and astrocytes. Transcriptomic alterations in microglia point to a reduced proinflammatory phenotype, associated to reduced resistance to oxidative stress and apoptosis, which was confirmed with immunohistochemical quantification of IBA1 density. Astrocytes show transcriptomic evidence of an imbalance of multiple metabolic pathways, extracellular matrix composition and downregulated immune signalling. These alterations are associated to ADCY2 and NCAN, two GWAS genes upregulated in astrocytes. Finally, cell-cell communication analysis prioritized upregulated SPP1-CD44 signalling to astrocytes as a potential regulator of the transcriptomic alterations in BD. Our results indicate that microglia and astrocytes are characterized by downregulated immune responses associated to a dysfunction of core mechanisms via which these cells contribute to brain homeostasis.

neuroscience↗

bioRxiv2023

Facile determination of the Poisson's ratio and Young's modulus of polyacrylamide gels and polydimethylsiloxane

Polyacrylamide hydrogels (PAH) and polydimethylsiloxane (PDMS) are two soft materials often used in cell mechanics and mechanobiology, in manufacturing lab-on-a chip applications, among others. This is partly due to the ability to tune their elasticity with ease, in addition to various chemical modifications. For affine polymeric networks, two (of three) elastic constants - the Youngs modulus (E), the shear modulus (G), and the Poissons ratio ({nu}) - describe the purely elastic response to external forces. However, the literature addressing the experimental determination of {nu} for PAH (also sometimes referred to as PAA gels in the literature) and PDMS is surprisingly limited when compared to the literature reporting values of E and G. Here, we present a facile method to obtain the Poisons ratio and Youngs modulus for PAH and PDMS based on static tensile tests, and cross-correlate these values with those obtained via a second independent method, shear rheology. We show that: i) the Poissons ratio may vary significantly from the value for incompressible materials ({nu} = 0.5), and ii) find a high degree of agreement between shear rheology and macroscopic static tension tests for PAH but not PDMS. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/540222v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@120116forg.highwire.dtl.DTLVardef@58acbcorg.highwire.dtl.DTLVardef@1b48683org.highwire.dtl.DTLVardef@eb3fda_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

Natural and engineered isoforms of the inflammasome adaptor ASC form non-covalent, pH-responsive hydrogels

The protein ASC polymerizes into intricate filament networks to assemble the inflammasome, a filamentous multiprotein complex that triggers the inflammatory response. ASC carries two Death Domains integrally involved in protein self-association for filament assembly. We have leveraged this behavior to create non-covalent, pH-responsive hydrogels of full-length, folded ASC by carefully controlling the pH as a critical factor in the polymerization process. We show that natural variants of ASC (ASC isoforms) involved in inflammasome regulation also undergo hydrogelation. To further demonstrate this general capability, we engineered proteins inspired in the ASC structure that successfully form hydrogels. We analyzed the structural network of the natural and engineered protein hydrogels using transmission and scanning electron microscopy, and studied their viscoelastic behavior by shear rheology. Our results reveal one of the very few examples of hydrogels created by the self-assembly of globular proteins and domains in their native conformation and show that Death Domains can be used alone or as building blocks to engineer bioinspired hydrogels.

bioengineering↗

bioRxiv2023

Antimicrobial Susceptibility Profile of Neisseria gonorrhoeae from Patients Attending a Medical Laboratory, Institut Pasteur de Madagascar between 2014-2020: Phenotypic and Genomic characterization in a Subset of Neisseria gonorrhoeae Isolates.

2The antimicrobial resistance of Neisseria gonorrhoea to all classes of current available antibiotics is a global concern. National surveillance programmes monitoring the susceptibility profiles of Neisseria gonorrhoeae hardly exist in resource constraint settings. Therefore, little is known about the antimicrobial susceptibility profile and associated genetic resistance mechanisms of N. gonorrhoeae in Madagascar. We report susceptibility data of N. gonorrhoeae isolates obtained by the medical laboratory of the Institut Pasteur de Madagascar, from 2014 -2020. In addition, we present data on the antimicrobial resistance mechanisms and antimicrobial resistance profile of a subset of isolates (N=46), including all isolates available of 2020. Over the study period, ceftriaxone resistant isolates exceeding the threshold of 5% in 2017 and 2020, were reported. Of the subset of re-tested isolates, all were found susceptible to ceftriaxone, azithromycin, and spectinomycin. Conversely, all isolates were resistant to ciprofloxacin and the majority was also resistant to penicillin and tetracycline. None of the isolates carried the mosaic penA gene and chromosomal mutations associated to the antibiotic resistance in gyrA, parC, penA, ponA, porB and mtrR genes were detected. The high rate of resistance to Penicillin and Tetracycline is explained by the presence of {beta}-lactamase blaTEM and tetM genes, respectively, a plasmid mediated resistance. We found a high number of circulating multilocus sequence types. Almost half of them were new types, and one of them was among the four most predominant sequence types. Our report provides a detailed dataset obtained through phenotypic and genotypic methods which will serve as baseline for future surveillance of N. gonorrhoeae in our setting, and Madagascar. 1.5 RepositoriesThis Whole Genome Shotgun project has been deposited at DDBJ/ENA/GenBank under the Accession BioProject PRJNA929018. 3 Impact statementNeisseria gonorrhoeae is becoming increasingly resistant to all classes of antibiotics available for infections treatment. Resource constraint settings encounter difficulties in implementing surveillance of the antimicrobial susceptibility of N. gonorrhoeae. We report here antimicrobial susceptibility results from gonorrhoea among patients consulting a medical laboratory in Antananarivo, Madagascar in 2014-2020. We used whole-genome sequencing to identify resistance mechanisms in a subset of isolates including all viable isolates of 2020. We report multilocus sequence types and discuss phenotypes and genotypes according to the phylogenetic analysis of the isolates. The susceptibility results are the first in a decade to be reported. We set the baseline to study further the evolution and transmission of N. gonorrhoeae resistance mechanisms and genotypes in general. Our report will enable improving surveillance of Neisseria gonorrhoeae in Madagascar and Africa. Overall, it will contribute to the global, regional, and national surveillance of N. gonorrhoeae. In addition, it may set a benchmark for implementation in other settings facing barriers implementing phenotypic resistance surveillance of N. gonorrhoeae. 4 Data summaryThe source code of the Tormes pipeline used in this study is also available on Github: https://github.com/nmquijada/tormes. The SRA sequences have been deposited in the NCBI SRA database under accession numbers SRR23260223 and SRR23260193. The genome assemblies can be accessed using the accession numbers: SAMN32949360 - SAMN32949405. The MLST genes of all isolates can be accessed through this link: https://doi.org/10.5281/zenodo.7581537 The Perl scripts used for a quality filtering of the assemblies which is to remove small contigs can be accessed through the following link: https://github.com/Alainnoah/Remove-Small-Contigs-Draft-Assemblies. Genomic analysis with metadata in Pathogenwatch could be accessed with this link: https://pathogen.watch/collection/f7t4wjtjlybh-mdgwhofa A visualization of genomic epidemiology of our isolates with Microreact can be accessed with this link: https://microreact.org/project/7FADQYwhm5h1zJyJTynM6R-unnamed-project A supplementary material in an Excel sheet summarizing the lists of plasmids used for alignment (Table S1), the statistics of the sequences (Table S2), and the minimum inhibitory concentration values of N. gonorrhoeae isolates and their antimicrobial resistance genetic mechanisms (Table S3) is available through this link: https://doi.org/10.6084/m9.figshare.21973511

microbiology↗

bioRxiv2023

How Interactions During Viral-Viral Coinfection Can Shape Infection Kinetics

Respiratory virus infections are a leading cause of disease worldwide with multiple viruses detected in 20-30% of cases and several viruses simultaneously circulating. Some infections with viral copathogens have been shown to result in reduced pathogenicity while other virus pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral-viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV) followed by influenza A virus (IAV) after 3 days. The results suggested that IAV reduced the rate of RSV production while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios not examined experimentally, including different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis showed that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to slower clearance of IAV infected cells by the other viruses. On the contrary, the improved outcome when IAV followed RV could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral-viral coinfections in this way provides new insights about how viral-viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation.

systems biology↗