Biology subjects

Franzenburg, S.

Publications and source records attributed to Franzenburg, S..

At least 19 recordsLinked to original sources

bioRxiv2025

Maternal transmission of a plastid structure enhances offspring fitness

Development in the sea has long been thought to be a nutritional gamble that disproportionately ends in starvation. Here, we unexpectedly show that components of plastids are incorporated into sea urchin eggs and that these, in turn, benefit developmental fitness. We find chromoplast-derived carotenoid crystals and chromoplast-specific metabolites inside of sea urchin eggs. The light-dependent activity of these chromoplast components influence the subsequent abundance of phytohormones that, in turn, regulate the use of energetic lipids that promote development and survival. Offspring that benefit from these chromoplast components are predicted to disperse further, over larger geographic areas, and use a wider range of currents, including those that cross ocean basins. Data presented here challenge the long-held assumption that components of non-metazoan organelles are unable to enter the germline and be passed between generations. We hypothesize that sea urchins manipulate plastids solely for their self-interest by a process that we term machioplasty, with the result of this process being a novel and adaptive form of maternal provisioning. SIGNIFICANCEMaking a fertilizable egg is a complex and carefully regulated process. One long-held assumption is that any component of non-animal organelles are unable to cross the evolutionary valley between non-reproductive and reproductive cells. Here, we unexpectedly show that components of plastids are incorporated into sea urchin eggs and that these, in turn, benefit developmental fitness. Offspring benefit from these plastid components by developing more quickly into larvae and having higher survival due to ability to use phytohormones that influence energetic lipids. This allows offspring to use a wider range of ocean currents, including those that cross entire basins. This challenge the long-held assumption that components of non-metazoan organelles are unable to be passed between generations.

developmental biology↗

bioRxiv2025

Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope

Antibiotic combination in time and space is a key strategy to combat antimicrobial resistance. The success of such treatment designs requires their robust efficacy across treatment conditions and a pathogens genomic diversity. This study found that an initial treatment with a {beta}-lactam antibiotic causes robust cellular sensitization towards an aminoglycoside antibiotic across the high-risk human pathogen Pseudomonas aeruginosa, including resistant strains. This phenomenon of cellular sensitization, termed negative hysteresis, is modulated by the Cpx envelope stress response system and linked to membrane stress during growth. The increase in efficacy is achieved through a {beta}-lactam induced elevated cellular uptake of the subsequently administered aminoglycoside. Negative hysteresis and the Cpx system are linked in several cases to the expression of synergistic drug interactions, thus enhancing efficacy of antibiotic combinations. Overall, our study identifies the phenomenon of negative hysteresis as a robustly inducible phenotype and thus a unique focus for optimizing antimicrobial therapy.

evolutionary biology↗

bioRxiv2025

Endocrine-enriched stem cell-derived islets improve long-term safety in vivo

Fully differentiated stem cell-derived islets (SC-islets) are proven to normalise blood glucose in type 1 diabetic patients. However, the presence of off-target cell types and the immature SC-islet function upon transplantation remain unresolved problems. Here, we established sorting strategies to generate SC-islets with defined glucagon-producing SC-- and insulin-producing {beta}-cell ratios and assessed their safety and efficacy in vitro and in vivo. Engineering SC-islets is beneficial to the insulin response in vitro, which does not translate to improved glycaemic regulation in vivo. Importantly, hormone-producing endocrine cell enrichment and thus off-target cell type depletion eliminated the risk for unwanted outgrowth in vivo. Single cell analysis defined off-target cells in vitro and in vivo and identified marker genes to assess SC-islet quality and define safety release criteria before graft transplantation. This study highlights the importance of determining the SC-islet composition and establishing rigorous quality controls to ensure long-term safety for {beta}-cell replacement therapy.

bioengineering↗

bioRxiv2025

Quantifying The Impact of Bulk TCR-Seq Methodological Choices on The Profiled T Cell Repertoire

Bulk T cell repertoire profiling using sequencing (TCR-Seq) is a powerful method to investigate T cell responses to natural infections, vaccines, cancers, and autoimmune diseases. This assay can be conducted using various techniques, such as multiplex PCR or 5-RACE. However, each methods introduces systematic biases that can result in different pictures of the underlying T cell repertoire. Furthermore, the impact of technical variables on the accuracy of these methods remains understudied. Thus, in this study, we systematically characterized different multiplex PCR-based protocols, focusing on the quality and quantity of the utilized RNA/DNA, extraction methods, amplification programs, variations between production batches, and technical handling of samples. Our findings highlight the important role of RNA/DNA quality in shaping the profiling results of T cell repertoires. Whereas low RNA/DNA quantities can be partially compensated for by increasing the number of PCR cycles, this is partially not possible with lower quality. In conclusion, our results highlight the influence of different technical choices on the biological conclusions drawn from TCR-Seq data and provide practical guidelines to finetune these variables to ensure consistent and reliable results under diverse experimental constraints.

immunology↗

bioRxiv2025

Multi-omics analysis highlights the link of aging-related cognitive decline with systemic inflammation and alterations of tissue-maintenance

Aging-related cognitive decline is associated with changes across different tissues and the gut microbiome, including dysfunction of the gut-brain axis. However, only few studies have linked multi-organ alterations to cognitive decline during aging. Here we report a multi-omics analysis integrating metabolomics, transcriptomics, DNA methylation, and metagenomics data from hippocampus, liver, colon, and fecal samples of mice, correlated with cognitive performance in the Barnes Maze spatial learning task across different age groups. We identified 734 molecular features associated with cognitive rank within individual data layers, of which 227 features remain when integrating all data layers with each other. Among the single-layer predictors, several host and microbial features were highlighted, with host-associated markers being predominant. Host features associated with cognitive function mainly belong to innate and adaptive inflammatory activity (inflammaging) and developmental processes. Our findings suggest that cognitive decline in aging is tightly coupled to systemic, age-associated inflammation, potentially initiated by microbiome-driven gastrointestinal inflammatory activity, emphasizing a link between peripheral tissue alterations and brain function.

systems biology↗

bioRxiv2025

Regulation of the transcriptome, miRNAs, and alternative splicing in a FSGS zebrafish injury model

BackgroundFocal Segmental Glomerulosclerosis (FSGS) is a severe kidney disorder with complex and not yet fully understood pathogenesis. Alternative splicing (AS) - the generation of distinct protein isoforms from the same gene - might play a critical role by the regulation of gene functions and disease development. MethodsTo investigate the role of AS in FSGS, we used a zebrafish model, which mimics key human FSGS features, including foot process effacement, matrix accumulation, podocyte detachment and parietal epithelial cell activation. We performed total RNA sequencing of isolated zebrafish glomeruli and whole larvae, followed by integrative bioinformatic analysis to identify AS events and regulatory miRNAs. ResultsOur data revealed a downregulation of essential podocyte genes (nphs1, nphs2, podxl, wt1) and an inhibition of pathways associated with nephron development and cytoskeletal organization. We also observed increased expression of the transcription factor stat3 and disease-associated miRNAs such as miR-21 and miR-193. AS analysis identified approximately [~]7,000 splicing events, primarily exon skipping ([~]80%), affecting genes such as nphs1, magi2, and ptpro. A total of 136 and 612 alternatively spliced genes were found at 5 and 6 days post-fertilization (dpf), respectively. Isoform switch analysis uncovered 70 genes affected by AS in FSGS, including epb41l5 (linked to podocyte adhesion), fgfr1a (fibroblast growth signaling), and members of the SRSF splicing factor family (e.g., srsf3a). ConclusionsThese findings emphasize the importance of transcriptional and post-transcriptional regulation, including AS, in FSGS pathogenesis. Furthermore, they support the zebrafish model as a valuable system for identifying novel mechanisms and potential therapeutic targets for kidney diseases.

cell biology↗

bioRxiv2025

JAK/STAT Signaling Governs Airway Epithelial Homeostasis and Stress Resilience in Drosophila

Airway epithelia must maintain barrier integrity while continuously adapting to changing environmental conditions. This requires key signaling pathways in airway epithelia to operate within a tightly controlled functional range. Here, we show that airway epithelial homeostasis in Drosophila depends on balanced JAK/STAT signaling. Basal pathway activity is constitutively present in differentiated epithelial cells and is necessary for cell survival, epithelial integrity and stress resistance. In accordance with this role as a stress responsive regulator in epithelial biology, environmental stressors, including hypoxia, cigarette smoke, and cold exposure, induce JAK/STAT signaling. In contrast, sustained pathway activation is associated with airway remodeling characterized by epithelial thickening, luminal narrowing, and altered cellular organization. Transcriptomic analysis reveals that sustained activation is associated with a coordinated epithelial stress program integrating immune signaling, proteostasis, and metabolic adaptation. Cross-species comparisons with murine and human datasets suggest that key aspects of this response are conserved. Pharmacological inhibition demonstrates that remodeling depends on continued pathway activity and can be partially reversed in vivo. Together, our findings support a model in which airway epithelial homeostasis depends on maintaining JAK/STAT signaling within a defined functional range. This "Goldilocks" principle provides a conceptual framework for understanding how epithelial stress responses are balanced under physiological and pathological conditions. Graphical abstract

cell biology↗

bioRxiv2025

Exogenous dsRNA made accessible to Dicer by two eukaryotic RNA-dependent RNA polymer-ases

Discrimination of self from non-self RNA is a critical requirement for any cell to respond to infections and to maintain cellular integrity. We report novel functions for two RNA-dependent RNA polymerases (RDRs) in Paramecium in the detection of exogenous RNA. In the RNA interference (RNAi) mechanism, RDRs are normally involved in the production of large amounts of secondary siRNAs in response to an initial primary siRNA. To characterize the function of RDRs in context of exogenous RNA recognition, we developed a novel dsRNA delivery system using dextran nanoparticles to deliver heteroduplex dsRNA to cells as food particles, mimicking the natural phagosomal entry pathway. Subsequent small RNA sequencing allows us to dissect siRNAs produced from exogenous RNA or RDR transcripts. Contrary to expectations of how dsRNA-induced silencing is triggered, our data show that Dicer is unable to directly cleave exogenous dsRNA while two RDRs are required for the initial steps of dsRNA-induced RNAi. Paradoxically, these two RDRs must replicate dsRNA to make it available for Dicer cleavage and primary siRNA accumulation. Our data also show that this system works efficiently also with exogenous ssRNA, although RDR2 is dispensable for ssRNA conversion. The function of RDRs in this protist is in contrast to that in animals, plants and fungi and extends the functional diversity of these polymerases. RDR-associated complexes appear to control the entry of food and symbiont-derived RNA into the RNAi machinery, enabling complex RNA interactions with the environment.

genetics↗

bioRxiv2025

Benchmarking porcine pancreatic ductal organoids for drug screening applications

Primary human pancreatic ductal organoids (HPDO) have emerged as a model to study pancreas biology and disease. Yet, donor material availability, and a lack of extensive benchmarking limits the range of applications. To address this gap, we established porcine pancreatic ductal organoids (PPDO) as a system from an easily obtainable source to model pancreatic ductal/progenitor biology. We benchmarked PPDO to HPDO and primary porcine pancreas using single-cell RNA sequencing (scRNA-Seq). We observed no overt phenotypic differences in PPDO derived from distinct developmental stages, with a WNT signaling enriched population characterizing PPDO. PPDO exhibited differentiation potential towards mature ductal cells and limited potential towards endocrine lineages. We used PPDO as a platform to assess the safety of FDA-approved drugs and showed conserved toxicity of statins and -adrenergic receptor inhibitors between PPDO and HPDO cultures. Overall, our results highlight the PPDO as a model for mammalian duct/progenitor applications.

developmental biology↗

bioRxiv2024

Entamoeba histolytica extracellular vesicles drive pro-inflammatory monocyte signaling

The parasitic protozoan Entamoeba histolytica secretes extracellular vesicles (EVs), but so far little is known about their function in the interaction with the host immune system. Infection with E. histolytica trophozoites can lead to formation of amebic liver abscesses (ALAs), in which pro-inflammatory immune responses of Ly6Chi monocytes contribute to liver damage. Men exhibit a more severe pathology as the result of higher monocyte recruitment and a stronger immune response. To investigate the role of EVs and pathogenicity in the host immune response, we studied the effect of EVs secreted by low pathogenic EhA1 and highly pathogenic EhB2 amebae on monocytes. Size and quantity of isolated EVs from both clones were similar. However, they differed in their proteome and miRNA cargo, providing insight into factors potentially involved in amebic pathogenicity. In addition, EVs were enriched in proteins with signaling peptides compared with the total protein content of trophozoites. Exposure to EVs from both clones induced monocyte activation and a pro-inflammatory immune response as evidenced by increased surface presentation of the activation marker CD38 and upregulated gene expression of key signaling pathways (including NF-{kappa}B, IL-17 and TNF signaling). The release of pro-inflammatory cytokines was increased in EV-stimulated monocytes and more so in male-than in female-derived cells. While EhA1 EV stimulation caused elevated myeloperoxidase (MPO) release by both monocytes and neutrophils, EhB2 EV stimulation did not, indicating the protective role of MPO during amebiasis. Collectively, our results suggest that parasite-released EVs contribute to the male-biased immunopathology mediated by pro-inflammatory monocytes during ALA formation. Author summaryParasites communicate with their host via small membranous extracellular vesicles (EVs) that can shuttle cargo and thus information between cells. The protozoan parasite Entamoeba histolytica releases EVs but not much is known about their role in the interaction with the host immune system. Infection with E. histolytica can lead to amebic liver abscess (ALA) formation. Innate immune cells, particularly monocytes, contribute to liver damage by releasing microbicidal factors. Men have a more severe ALA pathology as the result of a stronger monocyte immune response. In this study, we analyzed the effect of EVs from differently virulent E. histolytica clones on monocytes to better understand their interaction. EVs of both clones were similar in size and quantity but differed in their cargo, which provides information on factors potentially involved in pathogenicity. Monocytes responded to EVs of both clones in a pro-inflammatory manner that reflected the immune processes occurring during ALA in vivo, including the bias towards the male sex. Only EVs of amebae with low pathogenicity, and not those released by the highly pathogenic clone, elicited secretion of the granular enzyme myeloperoxidase, which plays a protective role during ALA. Overall, our data suggest that EVs may contribute to liver injury.

immunology↗

bioRxiv2024

RNA sequencing depth guidelines for the study of alternative splicing

A key parameter in the experimental design of RNA-seq projects is the choice of sequencing depth. Considering a limited budget, one needs to find a tradeoff between the number of samples and the sensitivity of the analysis, particularly concerning lowly expressed genes. While previous studies have proposed a lower bound for the comprehensive analysis of differential gene expression, for the analysis of alternative splicing, it has only been proposed for human adipose tissue. However, alternative splicing differs across tissues and conditions. We analyzed publicly available and newly generated deep-sequenced paired-end RNA-seq samples (between 150 and >500 million reads, read length 50-150 bp) from human buffy coat cells and diverse sets of tissues, including gluteal subcutaneous fat, heart, and hypothalamus. Our results show that the sequencing depth typically used in published cohorts is not sufficient to comprehensively capture the landscape of alternative splicing. This motivates the use of deeper sequencing or long-read technologies in future studies. Toward this goal, we offer guidelines for choosing a suitable sequencing depth. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/617406v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1aecd9org.highwire.dtl.DTLVardef@1b3d0fborg.highwire.dtl.DTLVardef@5d15c4org.highwire.dtl.DTLVardef@140035b_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

Sedentary life accelerates epigenetic ageing in King penguins

Introductory paragraphAdvances in medicine and food security have contributed to an increase in human lifespan1. Yet, the associated rise in sedentary behaviour and in obesity2,3 already threatens these gains4. Indeed, a growing body of evidence supports the central role of nutrient sensing and energy management pathways in regulating ageing rate and healthspan5,6, but the diversity of human lifestyles challenges our ability to identify the genetic and epigenetic drivers of this age acceleration. Here, we examine how the transition of wild King penguins to zoo husbandry can closely mimic the shift to a Western lifestyle in humans, and shed light on evolutionarily conserved epigenetic changes in responses to sedentary conditions. We show that, just like modern humans, zoo-housed King penguins experience an extended lifespan, but this comes at the cost of accelerated epigenetic ageing throughout life. This accelerated ageing is associated with differential methylation in key growth and maintenance pathways including the mTOR and PI3K/Akt networks, as well as in specific pathways of lipid-rich diet adaptation and heart-function. Our results demonstrate the deeply conserved link between sedentary behaviour and food availability on the one hand, and age acceleration on the other. Such evolutionary evidence may in turn help us to improve risk detection and, ultimately, therapeutics for lifestyle-induced age acceleration in humans7.

genomics↗

bioRxiv2024

The microbiota affects stem cell decision making in Hydra

Research on microbial communities colonizing animals has revealed that the microbiota, despite its typical containment to surfaces, influences virtually all organ systems of the host. In absence of a natural microbiota, the hosts development can be disturbed, but how developmental programs are affected by the microbiota is still poorly understood. Removing the microbiota from Hydra, a classic model animal in developmental biology, causes drastic developmental malformations and leads to polyps that temporarily lack the ability to bud. Recolonizing non-budding germfree Hydra with bacteria reverses this budding inhibition. Single-nucleus ATAC-seq detected a unique chromatin landscape associated with the non-budding phenotype. Single-cell RNA-seq and trajectory-based differential expression analysis showed that epithelial stem cell decision making is disturbed in non-budding polyps, whereby key developmental regulators are not expressed. This process is reversible by adding back bacteria. Transcriptionally silencing of one of the genes that failed to be activated in non-budding animals, GAPR1, led to polyps that have a significantly reduced budding capacity. The results show that maintaining a species-specific microbiota may enable the animal host to maintain its developmental program. Significance StatementAnimal developmental programs work within the context of coevolved associations with microbes. Here, we provide mechanistic evidence of the involvement of the microbiota in maintaining the pattern formation program of Hydra with the asexual formation of buds in the lower part of the body column. We demonstrate that in the absence of bacteria both the epigenetic and transcriptomic landscape is changed and that key regulatory factors are not expressed, causing changes in stem cell trajectories that result in loss of budding capacity. This study provides a new perspective on the role that microbiota plays during animal development and evolution. One Sentence SummaryMicrobiota interfere with Hydras asexual reproduction via modulating its stem cell differentiation programs.

developmental biology↗

bioRxiv2024

Phenotypic divergence associated with genomic changes suggest local adaptation in obligate asexuals

Local adaptation is a key evolutionary process that generates global biodiversity and is promoted by environmental heterogeneity. Most of the existing knowledge on adaptive capacity is focused on sexual organisms, while the adaptation potential of asexually reproducing eukaryotes as well as their vulnerability to environmental change remains unclear. Cyclical parthenogens of the keystone freshwater grazer Daphnia are known to be locally adapted with genetic differentiation related to environmental conditions even between neighbouring ponds. Similar patterns have been found in obligate parthenogenetic congeners, however studies on their local adaptation potential are rare. Here, we use respiration rate and whole genome sequencing to test the local adaptation of Arctic asexual polyploid Daphnia from lakes with contrasting oxygen environments. The genomic data revealed the presence of two genetic clusters which differed significantly in respiration rates, suggesting molecular evolution as an adaptive mechanism. Functional enrichment pointed to differences in metabolic processes between the two genetic clusters. Our results, combining phenotypic and whole genome sequencing data, suggest that these clones are locally adapted to low oxygen concentrations and provide support for local adaptation by evolution in an obligate parthenogen.

evolutionary biology↗

bioRxiv2024

Metatranscriptomics-based metabolic modeling of patient-specific urinary microbiome during infection

Urinary tract infections (UTIs) are a major health concern which incur significant socioeconomic costs in addition to substantial antibiotic prescriptions, thereby accelerating the emergence of antibiotic resistance. To address the challenge of antibiotic-resistant UTIs, our systems biology approach uncovers patient-specific uromicrobiome insights that are focused on community utilization of metabolites. By leveraging the distinct metabolic traits of patient-specific pathogens, we aim to identify metabolic dependencies of pathogens and provide suggestions for targeted interventions for future studies. Combining patient-specific metatranscriptomic data with genome-scale metabolic modeling and data from the Human Urine Metabolome, this study explores UTIs from a systems biology perspective through the reconstruction of tailored microbial community models to mirror the metabolic profiles of individual UTI patients urinary microbiomes. Delving into patient-specific bacterial gene expressions and microbial interactions, we identify metabolic signatures and propose mechanisms for UTI pathology. Our research underscores the potential of integrating metatranscriptomic data using systems biological approaches, providing insights into disease metabolic mechanisms and potential phenotypic manifestations. This contribution introduces a new method that could guide treatment options for antibiotic-resistant UTIs, aiming to lessen antibiotic use by combining the pathogens unique metabolic traits. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/586446v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1074251org.highwire.dtl.DTLVardef@192d45eorg.highwire.dtl.DTLVardef@b46927org.highwire.dtl.DTLVardef@638e2a_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract Metatranscriptome sequencing was used to investigate the functional uromicrobiome across a cohort of 19 individuals; patient-specific microbiome community models were reconstructed and simulated in a virtual urine environment. Total RNA was extracted from patients urine and sequenced to assess the metatranscriptome, providing insights into patient-specific uromicrobiome microbial taxa and their associated gene expression during urinary tract infections (UTIs). These combinatory datasets derived from metatranscriptomics data were further expanded first to reconstruct species specific metabolic models that were conditioned with gene expression. Gene expression conditioned metabolic models were combined in an in silico environment with a defined urine media to construct patient-specific context-specific uromicrobiome models, enabling an understanding of each patients unique microbiome. Using this approach, we aimed to identify patient-specific microbiome dynamics and provide insight towards various metabolic features that can be utilized or validated in future studies for individualized intervention strategies. Created with www.biorender.com. C_FIG

systems biology↗

bioRxiv2024

FoxO factors are essential for maintaining organ homeostasis by acting as stress sensors in airway epithelial cells

Airway epithelia must maintain functional and structural homeostasis despite exposure to diverse environmental stressors. FoxO transcription factors are well suited to this task, acting as integration hubs that translate extrinsic and intrinsic signals into appropriate physiological responses. We show that FoxO factors in Drosophila, mouse, and human airway epithelial cells (AECs) undergo nuclear translocation in response to stressors including hypoxia, temperature, and oxidative stress. In human airway epithelial cell lines, individual hFOXO factors show distinct, cell-type-specific activation patterns. In Drosophila, hypoxia was the only stressor among those tested that triggered a dfoxo-dependent innate immune response. Because Drosophila possesses a single FoxO ortholog, loss-of-function analysis directly demonstrated that dfoxo is required for stress resistance in the airway epithelium. Reduced FoxO expression was similarly observed in mouse models of asthma and in airway samples from asthma patients, paralleling the increased stress sensitivity seen upon FoxO loss in flies. While our data do not establish that reduced FOXO levels cause asthma, they indicate that FoxO-dependent stress pathways are altered in diseased airways across species. Together, these findings support a model in which FoxO coordinates adaptive epithelial stress responses that maintain airway homeostasis under environmental challenge.

physiology↗

bioRxiv2023

Transcriptomic responses of Mediterranean sponges upon encounter with seawater or symbiont microbial consortia

Sponges (phylum Porifera) constantly interact with microbes from the water column while filter-feeding and with the symbiotic partners they harbor within their mesohyl. Despite early observations on differential uptake between symbiont and seawater bacteria, it is still poorly understood how sponges discriminate between different microbial consortia. Initial evidence of the diverse repertoire of sponge immune receptors suggests their involvement in specific microbial recognition, yet experimental data is still scarce. We characterized the transcriptomic response of two sponge species, Aplysina aerophoba and Dysidea avara, upon incubation with two different microbial consortia, which were either enriched from ambient seawater or extracted from A. aerophoba. The sponges were sampled after 1 h, 3 h, and 5 h for RNA-Seq differential gene expression analysis. D. avara showed higher expression levels of genes related to immunity, ubiquitination, and signaling when incubated with A. aerophoba symbionts, than in incubations with seawater microbial consortia. Interestingly, the different bacteria consortia triggered changes in Nucleotide Oligomerization Domain (NOD)-Like Receptors (NLRs) gene expression in D. avara. We here provide the first experimental evidence for NLRs playing a role in distinguishing between different microbes in a sponge. In contrast, the response of A. aerophoba involved comparatively few genes and lacked genes encoding for immune receptors. This indicates that A. aerophoba is less responsive to microbial encounters than D. avara. Our study further reveals different transcriptomic responses between the two sponge species to microbes. The study of sponge responses to microbes aids in understanding the evolution of immune specificity and animal-microbe interactions. Significant statementAnimals rely on components of the immune system to recognize specific microbes, whether they are pathogens, food, or beneficial symbionts. However, in marine invertebrates, the mechanisms of microbial discrimination and specificity are not well understood. Our work suggests that:(i) the transcriptomic response by the sponge can be scaled according to the type of exposure, (ii) the response to microbial encounters is species-specific and (iii) NLRs seem to have a prominent role in the differential response to microorganisms, whether symbionts or food bacteria.

molecular biology↗

bioRxiv2023

Antibiotic prophylaxis and hospitalization of horses subjected to median laparotomy: gut microbiota trajectories and abundance increase of Escherichia

Horse clinics are hotspots for the accumulation and spread of clinically relevant and zoonotic multidrug-resistant bacteria, including extended-spectrum {beta}-lactamase producing (ESBL) Enterobacterales. Although median laparotomy in cases of acute equine colic is a frequently performed surgical intervention, knowledge about the effects of peri-operative antibiotic prophylaxis (PAP) based on a combination of penicillin and gentamicin on the gut microbiota is limited. Therefore, we collected fecal samples of horses from a non-hospitalized control group (CG) and from horses receiving either a pre-surgical single-shot (SSG) or a peri-operative 5-day (5DG) course of PAP. To assess differences between the two PAP regimens and the CG, all samples obtained at hospital admission (t0), on days three (t1) and ten (t2) after surgery, were screened for ESBL-producing Enterobacterales and subjected to 16S rRNA V1- V2 gene sequencing. We included 48 samples in the SSG (n=16 horses), 45 in the 5DG (n=15) and 20 in the CG (n=10). Two samples (6.5%) were positive for ESBL-producing Enterobacterales at t0 while this rate increased to 67% at t1 and decreased only slightly at t2 (61%). Shannon diversity index (SDI) was used to evaluate alpha-diversity changes, revealing that horses suffering from acute colic seemed to have a compromised fecal microbiota composition (5DG, SDImean of 5.90; SSG, SDImean of 6.17) when compared to the CG (SDImean of 6.53) at t0, although the difference lacked significance. Alpha-diversity decreased significantly in both PAP groups at t1, while at t2 the onset of microbiome recovery was noticed. Although we did not identify a significant SDImean difference with respect to PAP duration, the community structure (beta-diversity) was considerably restricted in samples of the 5DG at t1, most likely due to the ongoing administration of antibiotics. An increased abundance of Enterobacteriaceae, especially Escherichia, was noted for both study groups at t1. Further studies are needed to reveal important factors promoting the increase and residency of ESBL-producing Enterobacterales among hospitalized horses.

microbiology↗