Biology subjects

Gill, S.

Publications and source records attributed to Gill, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Djp1 is a multifunctional Hsp40 cochaperone for mitochondrial phospholipid metabolism

Mitochondria are cellular energy hubs best known for ATP production via oxidative phosphorylation; however, they also serve as biosynthetic centers for phospholipids. Mitochondrial phospholipids are critical for various cellular processes, and their loss underlies myriad mitochondrial diseases. The critical enzymes underlying these biosynthetic cascades are encoded in the nucleus, translated in the cytosol, and imported into mitochondria. Understanding of mechanisms and factors that ensure precise targeting of proteins to mitochondria has been long overlooked but remains critical. Recently, the J-protein/Hsp40 cochaperone Djp1 has emerged as a key player in mitochondrial protein targeting by promoting the transfer of precursors from the endoplasmic reticulum (ER) surface to mitochondria in a pathway termed ER-SURF. Molecular details regarding how Djp1 recognizes clients and more broadly supports mitochondrial function remain unknown. Using biochemical approaches, proteomics, and thin layer chromatography, we demonstrate that Djp1 is a regulator of Phosphatidylserine decarboxylase 1 (Psd1), an inner mitochondrial membrane resident responsible for mitochondrial phosphatidylethanolamine (PE) production. This regulation of Psd1 biogenesis is dependent on its mitochondrial targeting signal and is specific to Djp1 compared to other members of the Hsp40 family or ER targeting factors. Intriguingly, the combined loss of Djp1 and Psd1 results in a synthetic sick phenotype that unexpectedly reflects a role(s) for Djp1 in proper mitochondrial phospholipid metabolism independent of Psd1. Taken together, these findings expand our understanding of Djp1-dependent mitochondrial protein regulation and unveil Djp1 as important for mitochondrial phospholipid metabolism by multiple mechanisms.

cell biology↗

bioRxiv2026

Ischemia-Induced Post-Translational Modifications of GLT-1 Mediate Aberrant Trafficking and Impaired Glutamate Uptake

Glutamate transporters are essential for maintaining CNS homeostasis by clearing extracellular glutamate after synaptic transmission. Dysregulation of these transporters contributes to excitotoxicity in numerous neurological disorders, including ischemic stroke, making them a promising therapeutic target. However, the regulatory response of these transporters following ischemic insult remains poorly defined. In this work, using a model of oxygen-glucose deprivation in primary glia cultures, we report aberrant trafficking of the astrocytic glutamate transporter GLT-1 following ischemic insult. This response is characterized by increased transporter internalization and degradation, accompanied by reduced glutamate uptake capacity. Focusing on post-translational modifications (PTMs), we found that GLT-1 ubiquitination is markedly increased after ischemic insult and contributes to transporter internalization. Importantly, disrupting this ubiquitination interaction through mutation of C-terminal GLT-1 lysine residues restores GLT-1 surface expression and rescues glutamate uptake capacity through preventing early endosome 1 (EEA1)-mediated internalization. Additionally, we report that inhibition of C-terminal GLT-1 PTMs confers neuroprotection following ischemic insult in organotypic rat brain slices. Together, these findings demonstrate that ischemia-induced dysregulation of GLT-1 trafficking plays a critical role in impaired glutamate clearance and cellular recovery, highlighting GLT-1 ubiquitination as a potential therapeutic target for ischemic injury.

molecular biology↗

bioRxiv2025

scDNA: Single Cell DNA analysis software toolkit for subclonality discovery and assessment.

Advances in single cell multi-omics technologies have allowed for investigation into genotype-immunophenotype relationships and dynamic clonal changes in cancer patient samples. These technologies provide rich insights into genetic profiling, drivers of disease progression, and subclonal dynamics. Increased adoption and throughput of these technologies, necessitate accessible computational tools for processing and analysis. Toward developing easy to use computational tools, we introduce the Single Cell DNA (scDNA) package that allows for rapid analysis of single-cell molecular profiling. Our platform aims to provide a diagnostic summary tool for sample quality control, representative subclonal architecture within a sample, demultiplexing functionality for multi-sample processing, copy number variation, and mutation trajectory analysis to identify order of subclonal mutation acquisition. We showcase a series of vignettes on hematopoiesis datasets for each aim that reflects recently deployed uses of scDNA. Additionally, we show scDNA provides a modular, user-friendly framework that readily feeds into other standard software pipelines.

genomics↗

bioRxiv2025

Neuraminidase 3 acts in a rapid translation-based positive feedback loop to activate TGF-β1

Fibrosis appears to be an out-of-control wound healing response that drives a progressive formation of scar tissue in an organ. A key profibrotic cytokine, transforming growth factor beta-1 (TGF-{beta}1), upregulates levels of the fibrosis-driving sialidase, neuraminidase 3 (NEU3), and NEU3 can activate latent TGF-{beta}1 to release active TGF-{beta}1 from the sequestering LAP peptide. In the mouse bleomycin model of pulmonary fibrosis, NEU3 is both necessary and sufficient for fibrosis. In this report, we find that NEU3 levels increase both intracellularly and extracellularly in cultures of human lung fibroblasts within 5 minutes of TGF-{beta}1 exposure. This effect is driven by an increase in translation and is independent of new transcription, supporting a model where TGF-{beta}1 causes a pool of weakly translated NEU3 mRNA to increase translation. The RNA helicase DEAD-box helicase 3 (DDX3) mediates NEU3 translation. TGF-{beta}1 induces dephosphorylation of DDX3 within two minutes, and DDX3 inhibitors block the rapid NEU3 upregulation. The NEU3-TGF-{beta}1-NEU3 positive feedback loop is activated within 5 minutes, and the remaining LAP fragment (after NEU3 activation of the latent TGF-{beta}1 complex) appears to potentiate NEU3 upregulation. This feedback loop is blocked by NEU3 inhibitors. These findings suggest that NEU3 is a rapidly acting amplifier of TGF-{beta}1 signaling, likely through TGF-{beta}1-mediated dephosphorylation of DDX3, and this mechanism may be associated with an early tissue-healing response mechanism that drives the initiation and progression of fibrosis.

cell biology↗

bioRxiv2025

The neuroendocrine peptide catestatin promotes clearance of cutaneous Staphylococcus aureus through mast cell Mrgpr activation

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of cutaneous infections, underscoring the need for alternative therapeutic strategies. Catestatin, a neuroendocrine antimicrobial peptide produced by neurons and epithelial cells, has been implicated in skin defense against pathogens such as MRSA, though its mechanisms remain unclear. Here, we show that catestatin expression is upregulated in MRSA-infected skin wounds and that topical catestatin application significantly reduces MRSA burden in infected murine cutaneous wounds. This effect is dependent on the mast cell-specific G protein-coupled receptor Mrgprb2, the murine ortholog of human MRGPRX2. Notably, catestatin treatment leads to Mrgprb2-dependent suppression of inflammatory cytokine production and leukocyte infiltration, alongside upregulation of the antimicrobial peptide Defb14. In human mast cells, catestatin induces MRGPRX2-dependent degranulation, histamine release, prostaglandin D2 production, and cytokine expression. Pharmacological inhibition and western blot analysis reveal that catestatin activates multiple downstream G protein-dependent signaling pathways in an MRGPRX2-dependent manner. These findings demonstrate that catestatin promotes bacterial clearance by activating mast cells through Mrgprb2, thereby enhancing antimicrobial peptide production. Our study positions catestatin as a promising mast cell-targeting immunotherapeutic candidate for treating antibiotic-resistant skin infections.

immunology↗

bioRxiv2025

KLHL41 orchestrates sarcomere assembly and size to drive skeletal muscle hypertrophy in vivo

Sarcomere assembly and growth are fundamental processes essential for the development, function, and repair of skeletal muscle. However, the mechanisms underlying sarcomere formation and assembly in vivo, which are critical for the formation of functional myofibers in vertebrates, remain poorly understood. Defects in sarcomeres contribute to muscle dysfunction in numerous genetic and acquired myopathies, yet the lack of a clear understanding of specific sarcomeric defects has hindered the development of effective therapies. Nemaline myopathy (NM) is caused by mutations in genes that primarily affect sarcomere structure and function. The disease is clinically heterogeneous, with the congenital form being the most severe. Using zebrafish models of congenital forms of NM, we investigated sarcomere assembly in vivo during skeletal muscle development to identify key steps contributing to myofibril formation and muscle growth under both normal and disease conditions. Our findings demonstrate that the gene encoding the sarcomeric protein KLHL41 plays a critical role in the formation and directional organization of new sarcomeres within developing myofibrils, facilitating both radial and longitudinal muscle growth. Dysregulation of sarcomeric proteins and impaired protein turnover in the KLHL41-NM zebrafish model resulted in the development of sarcomeric defects. Moreover, we show that the interaction between the KLHL41-troponin complex is essential for muscle growth and cross-bridge regulation in developing muscle. These studies address a significant gap in the understanding of sarcomeric defects in myopathies and will help guide the development of targeted therapies aimed at rescuing these processes.

genetics↗

bioRxiv2025

Spatiotemporal dynamics of cryptococcal infection reveal novel immune modulatory mechanisms and antifungal targets

The threat and incidence of fungal diseases are increasing, as is the severity and mortality rates associated with these infections. New strategies to combat fungal infections are urgently needed to overcome rising rates of resistance and the emergence of new pathogens. To promote invasion within a host, fungi use highly adapted and regulated virulence factors, and, in turn, the host adopts an active and dynamic immune response to suppress infection. Understanding the interplay between these processes is crucial to move fungal disease management and treatment forward and improve global health outcomes. Within the present study, we tackle these challenges using state-of-the-art mass spectrometry instrumentation to explore proteome remodeling during active infection of Cryptococcus neoformans at an unprecedented depth with spatiotemporal resolution. Our prioritization of three host organs (i.e., lungs, brain, spleen) critical to initiation, progression, and response of disease discovers tissue-specific remodeling across time. Within the lungs, we revealed early and sustained activation of the host immune response integrated with characterization of a promising new antifungal target, and we propose the discovery of a competitive inhibitor for functional target disruption. Within the brain, proteome remodeling aligns with disease progression, and we define a new mechanistic role for haptoglobin in fungal cell modulation, as well as showcasing an adaptive survival response of C. neoformans within an hypoxic environment. Within the spleen, we reveal new dynamics of immune system activation upon cryptococcal infection. Overall, we provide the deepest integrated view of cryptococcal disease dynamics across temporal and spatial scales, revealing unrecognized mechanisms of host immunity and fungal pathogenesis that offer new avenues for targeted therapeutic intervention and disease management.

microbiology↗

bioRxiv2025

Divergent Hox cluster collinearity in horned beetles reveals adult head patterning function of labial

Hox genes play critical roles in specifying the regionalization of the body axis across metazoa, with the exception of the anterior dorsal head of bilaterian animals, which instead is instructed by a deeply conserved set of non-Hox regulators. The anterior dorsal head is also a hot spot of evolutionary diversification, raising the question as to the developmental-genetic underpinnings of such innovation. Onthophagine dung beetles develop evolutionarily novel and highly diversified horns on the dorsal head used as weapons during intrasexual conflicts. Preliminary RNAseq data unexpectedly documented Hox gene expression in the dorsal head of premetamorphic onthophagine larvae. Motivated by this observation, we aimed to (i) investigate the genomic content and arrangement of the Hox cluster across three onthophagine species, and (ii) assess expression patterns and (iii) potential functions of the anterior Hox genes labial, proboscipedia, and Deformed in patterning the adult beetle head and cephalic horns. We document an unexpected, derived Hox cluster configuration in the Onthophagus sagittarius genome, a species with apomorphic cephalic horn morphology. Yet despite this genomic rearrangement, embryonic expression patterns of labial and proboscipedia as well as the adult segment patterning functions of proboscipedia and Deformed were found to be conserved. In contrast, labial RNAi revealed an adult head patterning function outside horn-forming regions previously undescribed for any insect. Lastly, we show that electrosurgical ablation of the presumptive larval labial-expressing head region phenocopies this conspicuous adult labial RNAi defect. We discuss the implications of these data for current models of insect head development and diversification.

developmental biology↗

bioRxiv2024

Replicating retroviral delivery of an IL-15 superagonist improves antitumor immunity and long-term survival in poorly immunogenic glioblastoma models

Glioblastoma (GBM) is the most lethal primary brain neoplasm due to its highly immunosuppressive microenvironment and resistance to conventional therapies. To overcome this challenge, we engineered a replicating retrovirus (RRV) to deliver a superagonist interleukin-15 receptor-linked fusion protein (RLI) directly to tumor cells, engineering them into local immunotherapy biofactories. This strategy leverages the tumor-selective replication of RRV to achieve localized and sustained RLI expression within the tumor microenvironment. In two orthotopic poorly immunogenic GBM mouse models, intratumoral administration of RRV RLI significantly reduced tumor growth and prolonged survival compared to controls, with some mice achieving long-term remission and demonstrating immunologic memory upon rechallenge. Transcriptomic and flow cytometric analyses revealed that RRV RLI treatment enhanced infiltration and activation of CD8 T cells, NK cells, and upregulated antigen presentation pathways within the tumor microenvironment. Depletion studies indicated that the therapeutic efficacy of RRV RLI is dependent on both CD4 and CD8 T cells. Notably, combining RRV RLI with the GBM standard of care chemotherapeutic agent temozolomide (TMZ) synergistically improved survival outcomes. Subsequent single-cell RNA and T cell receptor sequencing identified enhanced effector cell activation, antigen presentation, and clonal T cell expansion in the combination therapy group. Further T cell receptor analysis and clustering implied a tumor-specific immune response rather than one targeting the viral delivery vehicle, suggesting that this therapeutic approach could be reapplied without eliciting anti-vector immunity. Our findings suggest that RRV-mediated delivery of RLI effectively transforms GBM tumors into immunostimulatory hubs, eliciting a potent anti-tumor immune response. This novel viral immunotherapy holds significant promise for clinical translation in the treatment of GBM and other difficult-to-treat solid tumors.

cancer biology↗

bioRxiv2024

Affective Symptoms in Pregnancy are Associated with the Vaginal Microbiome

Composition of the vaginal microbiome in pregnancy is associated with adverse maternal, obstetric, and child health outcomes. Identifying the sources of individual differences in the vaginal microbiome is therefore of considerable clinical and public health interest. The current study tested the hypothesis that vaginal microbiome composition during pregnancy is associated with an individuals experience of affective symptoms and stress exposure. Data were based on a prospective longitudinal study of a diverse and medically healthy community sample of 275 mother-infant pairs. Affective symptoms and stress exposure and select measures of associated biomarkers (diurnal salivary cortisol, serum measures of sex hormones) were collected at each trimester; self-report, clinical, and medical records were used to collect detailed data on socio-demographic factors and health behavior, including diet and sleep. Vaginal microbiome samples were collected in the third trimester (34-40 weeks) and characterized by 16S rRNA sequencing. Identified taxa were clustered into three community state types (CST1-3) based on dissimilarity of vaginal microbiota composition. Results indicate that depressive symptoms during pregnancy were reliably associated with individual taxa and CST3 in the third trimester. Prediction of functional potential from 16S taxonomy revealed a differential abundance of metabolic pathways in CST1-3 and individual taxa, including biosynthetic pathways for the neuroactive metabolites, serotonin and dopamine. With the exception of bioavailable testosterone, no significant associations were found between symptoms- and stress-related biomarkers and CSTs. Our results provide further evidence of how prenatal psychological distress during pregnancy alters the maternal-fetal microbiome ecosystem that may be important for understanding maternal and child health outcomes. ImportancePrenatal affective symptoms and stress are associated with maternal, obstetric, and child health outcomes, but the mechanisms underlying these links and their application to intervention remain unclear. The findings from this investigation extend prior microbiome-oriented research by demonstrating that the maternal vaginal microbiome composition has a biologically plausible mechanistic link with affective symptoms that also suggest additional clinical applications for assessment and intervention.

microbiology↗

bioRxiv2024

Enhanced delivery of protein therapeutics with a diphtheria toxin-like platform that evades pre-existing neutralizing immunity

Targeted intracellular delivery of therapeutic peptides and proteins remains an important but unresolved goal in biotechnology. A promising approach is to engineer bacterial exotoxins that deliver their cytotoxic enzymes into cells and can be engineered to target cancer cells as is the case with immunotoxins. The well-studied diphtheria toxin translocation domain is ideally suited as a delivery platform as it has been shown to be capable of delivering a wide range of macromolecular cargo. Widespread deployment of DT-based therapeutics in humans, however, is complicated by the prevalence of pre-existing anti-DT antibodies from childhood vaccinations that reduce the exposure, efficacy and safety of this important class of protein drugs. Thus, there is a great need for delivery platforms with no pre-existing immunity in humans. Here, we describe the discovery and characterization of a distant diphtheria toxin homolog from the ancient reptile pathogen Austwickia chelonae that we have named Chelona Toxin (CT). We show that CT is comparable to DT structure and function in all respects except that it is not recognized by pre-existing anti-DT antibodies present in human sera. Moreover, we demonstrate that the CT translocase is superior to the DT translocase at delivering therapeutic protein cargo into target cells. These findings highlight CT as a potentially class-enabling new chassis for developing safer and more efficacious immunotoxins and intracellular protein delivery platforms for cancer therapy.

biochemistry↗

bioRxiv2023

Optimizing PCR using mtDNA Universal Primers for Detecting Indigenous Domestic Animal Species from Pakistan

The prevalence of specific animal meat consumption is integral to human nutrition but is jeopardized by the widespread issue of meat adulteration, posing threats to both the industry and consumer health. Escalating demand has led to fraudulent practices, necessitating reliable techniques for authentic source identification, aligning with ethical and religious principles. PCR has proven effective in addressing this concern by examining twelve domestic animal species in Pakistan, differentiating between halal and haram species. The method employs universal primers for 16S rRNA gene amplification, generating species-specific DNA fragments. This sophisticated approach, producing distinct fragments for cow, camel, goat, sheep, chicken, cat, dog, donkey, duck, rabbit, horse, and human with 507, 385, 787, 763, 470, 700, 370, 600, 500, 750, 800 and 300bp holds promise for identifying and tracing these species in commercial meat products. By ensuring robust food traceability, this methodology combats contemporary challenges in adulteration, preserving the integrity of the food supply chain.

genetics↗

bioRxiv2023

Glioblastoma induces the recruitment and differentiation of hybrid neutrophils from skull bone marrow

Tumor-associated neutrophil (TAN) effects on glioblastoma biology remain under-characterized. We show here that hybrid neutrophils with dendritic features - including morphological complexity, expression of antigen presentation genes, and the ability to process exogenous peptide and stimulate MHCII-dependent T cell activation - accumulate intratumorally and suppress tumor growth in vivo. Trajectory analysis of patient TAN scRNA-seq identifies this phenotype as a polarization state which is distinct from canonical cytotoxic TANs and differentiates intratumorally from immature precursors absent in circulation. Rather, these hybrid-inducible immature neutrophils - which we identified in patient and murine glioblastomas - arise from local skull marrow. Through labeled skull flap transplantation and targeted ablation, we characterize calvarial marrow as a potent contributor of antitumoral myeloid APCs, including hybrid TANs and dendritic cells, which elicit T cell cytotoxicity and memory. As such, agents augmenting neutrophil egress from skull marrow - such as intracalvarial AMD3100 whose survival prolonging-effect in GBM we demonstrate - present therapeutic potential.

cancer biology↗

bioRxiv2023

Multi-omic screening of invasive GBM cells in engineered biomaterials and patient biopsies reveals targetable transsulfuration pathway alterations

While the poor prognosis of glioblastoma arises from the invasion of a subset of tumor cells, little is known of the metabolic alterations within these cells that fuel invasion. We integrated spatially addressable hydrogel biomaterial platforms, patient site-directed biopsies, and multi-omics analyses to define metabolic drivers of invasive glioblastoma cells. Metabolomics and lipidomics revealed elevations in the redox buffers cystathionine, hexosylceramides, and glucosyl ceramides in the invasive front of both hydrogel-cultured tumors and patient site-directed biopsies, with immunofluorescence indicating elevated reactive oxygen species (ROS) markers in invasive cells. Transcriptomics confirmed upregulation of ROS-producing and response genes at the invasive front in both hydrogel models and patient tumors. Amongst oncologic ROS, hydrogen peroxide specifically promoted glioblastoma invasion in 3D hydrogel spheroid cultures. A CRISPR metabolic gene screen revealed cystathionine gamma lyase (CTH), which converts cystathionine to the non-essential amino acid cysteine in the transsulfuration pathway, to be essential for glioblastoma invasion. Correspondingly, supplementing CTH knockdown cells with exogenous cysteine rescued invasion. Pharmacologic CTH inhibition suppressed glioblastoma invasion, while CTH knockdown slowed glioblastoma invasion in vivo. Our studies highlight the importance of ROS metabolism in invasive glioblastoma cells and support further exploration of the transsulfuration pathway as a mechanistic and therapeutic target.

cancer biology↗

bioRxiv2022

The Streptococcus mutans Rhamnose-glucose Polysaccharide Plays an Important Role in Oxidative Stress Resistance and Iron Homeostasis

The rhamnose-glucose polysaccharide (RGP) of Streptococcus mutans is known to play an essential role in cell division and biofilm formation. It has become increasingly apparent that the structure plays a role in protection against external stress, including an undefined role in oxidative stress. In this study, we demonstrate that the loss of RGP impairs the uptake of glucose and the susceptibility of S. mutans to lethal concentrations of iron, while at the same time, generates elevated content of intracellular iron, a prominent producer of reactive oxygen species. Intracellular iron levels were significantly higher in a strain lacking rhamnose production ({Delta}rmlD), compared to a strain deficient in components of the RGP production pathway ({Delta}rgpG). The seemingly paradoxical discrepancy between iron uptake and iron susceptibility may be partially explained by increased expression of dpr and sod, genes that protect against oxidative stress and prime S. mutans against oxidative stressors such as H2O2 and superoxide. Analysis of the promoter of the rhamnose biosynthesis gene rmlD indicated the presence of regulatory motifs, including Rex and PerR, which we have shown control expression for the genes responsible for rhamnose biosynthesis and RGP production. These results provide initial insights into the role that RGP plays in toleration of oxidative stress and suggest a complexity in regulation of the genes responsible for production of the RGP. ImportanceDental caries, a disease caused by Streptococcus mutans, imposes significant healthcare burdens and productivity losses in the US. The outer structure of S. mutans, which is primarily composed of the rhamnose-glucose polysaccharide (RGP), is understudied, though it plays a crucial role in survival of the organism in response to environmental stress. Elucidating the protective role of RGP and the regulatory mechanisms that control the synthesis of RGP in S. mutans will lead to insights into the structure and function of cell wall polysaccharides in other streptococci. This study reveals a role for L-rhamnose, the building block of RGP, in mediating homeostasis of iron uptake, while the loss of rhamnose biosynthesis causes alterations in transcription of sod and dpr.

microbiology↗

bioRxiv2022

Complement-dependent loss of inhibitory synapses on pyramidal neurons following Toxoplasma gondii infection

The apicomplexan parasite Toxoplasma gondii has developed mechanisms to establish a central nervous system infection in virtually all warm-blooded animals. Acute T. gondii infection can cause neuroinflammation, encephalitis, and seizures. Meanwhile, studies in humans, non-human primates, and rodents have linked chronic T. gondii infection with altered behavior and increased risk for neuropsychiatric disorders, including schizophrenia. We previously demonstrated that T. gondii infection triggers the loss of perisomatic inhibitory synapses, an important source of inhibition on excitatory pyramidal cells, and a type of synapse that is disrupted in neurological and neuropsychiatric disorders. Similar to other instances of inflammation and neurodegeneration, we showed that phagocytic cells (including microglia and infiltrating monocytes) contribute to the loss of these inhibitory synapses. However, in the case of T. gondii-induced synapse loss, phagocytic cells target and ensheath the cell bodies of telencephalic neurons. Here, we show that these phagocytic cells specifically ensheath excitatory pyramidal neurons, leading to the preferential loss of perisomatic synapses on these neurons. In contrast, inhibitory cortical interneuron subtypes are not extensively ensheathed by phagocytic cells following infection. Moreover, we show that infection induces expression of complement C3 protein by these excitatory neurons and that C3 is required for the loss of perisomatic inhibitory synapses, albeit not through activation of the classical complement pathway. Together, these findings provide evidence that T. gondii infection induces changes in excitatory pyramidal neurons that trigger selective removal of inhibitory perisomatic synapses in the infected neocortex and provide a novel role for complement in remodeling of inhibitory circuits in the infected brain.

neuroscience↗

bioRxiv2021

The effects of a synthetic and biological surfactant on the community composition and metabolic activity of a freshwater biofilm

Surfactants are used to control microbial biofilms in industrial and medical settings. Their known toxicity on aquatic biota and their longevity in the environment has encouraged research on biodegradable alternatives such as rhamnolipids. While previous research has investigated the effects of biological surfactants on single species biofilms, there remains a lack of information regarding the effects of synthetic and biological surfactants in freshwater ecosystems. We conducted a mesocosm experiment to test how the surfactant sodium dodecyl sulphate (SDS) and the biological surfactant rhamnolipid altered community composition and metabolic activity of freshwater biofilms. Biofilms were cultured in the flumes using lake water from Lake Lunz in Austria, under high (300 ppm) and low (150 ppm) concentrations of either surfactant over a four-week period. Our results show that both surfactants significantly affected microbial diversity. Up to 36% of microbial operational taxonomic units were lost after surfactant exposure. Rhamnolipid exposure also increased the production of the extracellular enzymes, leucine aminopeptidase and glucosidase, while SDS exposure reduced leucine aminopeptidase and glucosidase. This study demonstrates that exposure of freshwater biofilms to chemical and biological surfactants caused a reduction of microbial diversity and changes in biofilm metabolism, exemplified by shifts in extracellular enzyme activities. Key PointsO_LIMicrobial biofilm diversity decreased significantly after surfactant exposure. C_LIO_LIExposure to either surfactant altered extracellular enzyme activity. C_LIO_LIOverall metabolic activity was not altered, suggesting functional redundancy. C_LI

microbiology↗

bioRxiv2020

A systems genomics approach uncovers molecular associates of RSV severity

Globally, RSV infection results in millions of hospitalizations and thousands of deaths each year. Specific factors that contribute to disease severity, such as premature birth and certain comorbidities, are well established. Additionally, genetic variants resulting in alterations in the adaptive and innate immune response appear to be associated with RSV severity. While previous studies focused on a single aspect of the disease, we jointly modeled the association of disparate data modalities with RSV severity. To investigate the host response to respiratory syncytial virus (RSV) infection in infants, we performed a systems-level study of RSV pathophysiology, incorporating high-throughput measurements of the peripheral innate and adaptive immune systems and the airway epithelium and microbiota. Specifically, we developed and employed a novel multi-omic data integration method based on multilayered principal component analysis, penalized regression, and feature weight back-propagation. Our novel approach enabled us to identify cell type specific and shared cellular pathways associated with RSV severity. Of particular interest was the association between RSV severity, activation of pathways controlling Th17 and acute phase response signaling, and inhibition of B cell receptor signaling, which were present in both airway and immune cells. These data identify specific aspects of dysregulation between the humoral and mucosal response to RSV that may play a critical role in determining illness severity.

genomics↗