The impact of acute low salinity stress on Antarctic echinoderms.

Climate change is causing increased coastal freshening in Antarctica, leading to reduced salinity. For Antarctica's endemic echinoderms, adapted to the stable polar environment, the impact of rapid reductions in coastal salinity on physiology and behaviour is currently unknown. Six common Antarctic echinoderms (the sea urchin Sterechinus neumayeri; the sea star Odontaster validus; the brittle star Ophionotus victoriae; and three sea cucumbers Cucumaria georgiana, Echinopsolus charcoti and Heterocucumis steineni), were directly transferred from ambient salinity (34.5‰) to a range of salinity dilutions (29-9‰) for 24 h. All species showed reduced activity and the establishment of a temporary osmotic gradient between coelomic fluid and external seawater. Most species exhibited a depression in oxygen consumption across tolerated salinities; however, at very low salinities that later resulted in mortality, oxygen consumption increased to levels comparable to those at ambient. Low salinity tolerance varied substantially between species, with O. victoriae being the least tolerant (24 h LC50 (lethal for 50% of animals) = 19.9‰) while E. charcoti and C. georgiana demonstrated the greatest tolerance (24 h LC50 = 11.5‰). These findings demonstrate the species-specific response of Antarctica's endemic echinoderms to short-term hypoosmotic salinity events, providing valuable insight into this phylum's ability to respond to an underreported impact of climate change.

Population characteristics and predation rates of the dominant soft-bodied and durophagous predators on temperate intertidal shores.

Substantial research exists on predation and its ecology. Most research has focused on durophagous fishes, brachyuran crabs, and lobsters. Data are lacking, however, on soft-bodied predators like anemones, and their contribution to overall levels of predation remains largely unevaluated. Here, we compared predation rates of the durophagous predator, the crab C. maenas and the soft-bodied predator, the anemone Actinia equina on 15 intertidal shores around Anglesey, north Wales, UK. We employed a novel approach to assess predation based on measuring faecal output from recently collected individuals and converting it to food consumed using absorption efficiencies (AEs) measured using potential prey species inhabiting the same shores. Anemone mean abundance was 8.21 (± 0.27, s.e.) individuals.m-2, whereas for C. maenas it was 0.23 (± 0.02, s.e.) individuals.m-2. AEs when fed mussel tissue, a polychaete worm, or a shrimp were 92.8-94.0% in C. maenas and 40.5-95.8% in A. equina. This difference in values reflected the different feeding modes of the two predators. Unexpectedly, A. equina consumed 3.5-7 times more prey than C. maenas. The consumption of larger amounts of prey by an anemone than the dominant durophagous predator has important consequences for calculating energy flows in food webs, understanding predation controls in assemblages, and potentially for wider predation trends.

Why do students choose to do an extended GP placement?

The drivers for medical students' decision making when considering which Student Selected Component (SSC) to undertake is poorly understood. Furthermore, it is unclear why students undertake a specific SSC allowing them to have an extended placement in GP in their final year. It is known that high quality GP placements encourage students to subsequently choose GP as their career, therefore if the decision-making process of students in this area can be better understood, then this may help inform medical school actions to encourage a greater uptake of these extended placements.Semi-structured interviews were conducted with final year medical students at a Scottish University. Students were selected to provide a mixture of those who had and had not chosen to undertake the extended placement. The data was transcribed and analysed using thematic analysis to generate themes which represented the data.This showed that career intention was a major factor driving SSC choice. Additionally, students sought peer feedback and tended to avoid specific SSCs if they felt a lack of internal motivation. Considering the choice for the extended placement, students tended, again, to choose based on career intentions, and they also based their decision on previous experiences of GP.Career intention and prior experience are key factors in student choice of SSC and whether to undertake an extended GP. In order to address the national shortage of GPs medical schools need to consider how they might influence these drivers.

Ocean warming and acidification adjust inter- and intra-specific variability in the functional trait expression of polar invertebrates.

Climate change is known to affect the distribution and composition of species, but concomitant alterations to functionally important aspects of behaviour and species-environment relations are poorly constrained. Here, we examine the ecosystem ramifications of changes in sediment-dwelling invertebrate bioturbation behaviour-a key process mediating nutrient cycling-associated with near-future environmental conditions (+ 1.5 °C, 550 ppm [pCO2]) for species from polar regions experiencing rapid rates of climate change. We find that responses to warming and acidification vary between species and lead to a reduction in intra-specific variability in behavioural trait expression that adjusts the magnitude and direction of nutrient concentrations. Our analyses also indicate that species behaviour is not predetermined, but can be dependent on local variations in environmental history that set population capacities for phenotypic plasticity. We provide evidence that certain, but subtle, aspects of inter- and intra-specific variation in behavioural trait expression, rather than the presence or proportional representation of species per se, is an important and under-appreciated determinant of benthic biogeochemical responses to climate change. Such changes in species behaviour may act as an early warning for impending ecological transitions associated with progressive climate forcing.

The SAGES masters program presents the 10 seminal articles for laparoscopic sleeve gastrectomy.

BACKGROUND: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program includes eight distinct clinical pathways. The Bariatric Surgery Pathway focuses on three anchoring procedures, including the laparoscopic sleeve gastrectomy (LSG) which is the most commonly performed bariatric procedure in the United States. In this article, we present and discuss the top 10 seminal articles regarding the LSG. METHODS: The literature was systematically searched to identify the most cited papers on LSG. The SAGES Metabolic and Bariatric Surgery committee reviewed the most cited article list, and using expert consensus elected the seminal articles deemed most pertinent to LSG. These articles were reviewed in detail by committee members and are presented here. RESULTS: The top 10 most cited sentinel papers on LSG focus on operative safety, outcomes, surgical technique, and physiologic changes after the procedure. A summary of each paper is presented, including expert appraisal and commentary. CONCLUSIONS: The seminal articles presented support the widespread acceptance and use of the LSG by bolstering the understanding of its mechanism of action and by demonstrating its safety and excellent patient outcomes. All bariatric surgeons should be familiar with these 10 landmark articles.

Trajectory of increased iceberg kill-off in West Antarctica's shallows.

Compared with low latitude coasts, many polar latitudes are still little impacted by intense and direct anthropogenic stressors. Climate forcing is now bringing rapid physical change to nearshore polar realms. In the shallow coastal waters adjacent to the United Kingdom's Rothera Research Station in the West Antarctic Peninsula (WAP), 225 seabed markers at 5-25 m depth have been surveyed and replaced every year from 2002-2023 (75 markers at each of 5, 10 and 25 m). This is one of the longest continuously running marine disturbance experiments in the world, in one of Earth's fastest changing environments. Different categories of sea ice are recorded (including when the sea surface freezes into fast ice) at Rothera since the 1980s, and losses of marine ice in both polar regions are one of the striking responses to a warming planet1. Five to ten years of seabed marker hit rate data (marker broken or moved) showed that reduced sea ice cover is correlated with disturbance and mortality on the seabed2,3.

A comparative study of tissue protein synthesis rates in an Antarctic, Harpagifer antarcticus and a temperate, Lipophrys pholis teleost.

The affect of temperature on tissue protein synthesis rates has been reported in temperate and tropical, but not Antarctic fishes. Previous studies have generally demonstrated low growth rates in Antarctic fish species in comparison to temperate relatives and elevated levels of protein turnover. This study investigates how low temperatures effect tissue protein synthesis and hence tissue growth in a polar fish species. Groups of Antarctic, Harpagifer antarcticus and temperate, Lipophrys pholis, were acclimated to a range of overlapping water temperatures and protein synthesis was measure in white muscle (WM), liver and gastrointestinal tract (GIT). WM protein synthesis rates increased linearly with temperature in both species (H. antarcticus 0.16-0.23%.d-1, L. pholis, 0.31-0.76%.d-1), while liver (H. antarcticus 0.24-0.27%.d-1, L. pholis, 0.44-1.03%.d-1) and GIT were unaffected by temperature in H. antarcticus but increased non-linearly in L.pholis (H. antarcticus 0.22-0.26%.d-1, L. pholis, 0.40-0.86%.d-1). RNA to protein ratios were unaffected by temperature in H. antarcticus but increased weakly, in L.pholis WM and liver. In L.pholis, RNA translational efficiency increased significantly with temperature in all tissues, but only in liver in H. antarcticus. At the overlapping temperature of 3 °C, protein synthesis (WM 26%, Liver, 39%, GIT, 35%) and RNA translational efficiency (WM 273%, Liver, 271%, GIT, 300%) were significantly lower in H. antarcticus than L.pholis, while RNA to protein ratios were significantly higher (WM 270%, Liver 170%, GIT 186%). Tissue specific effects of temperature are detectable in both species. This study provides the first evidence, that tissue protein synthesis rates are constrained in Antarctic fishes.

Testing the Resilience, Physiological Plasticity and Mechanisms Underlying Upper Temperature Limits of Antarctic Marine Ectotherms.

Antarctic marine ectotherms live in the constant cold and are characterised by limited resilience to elevated temperature. Here we tested three of the central paradigms underlying this resilience. Firstly, we assessed the ability of eight species, from seven classes representing a range of functional groups, to survive, for 100 to 303 days, at temperatures 0 to 4 °C above previously calculated long-term temperature limits. Survivors were then tested for acclimation responses to acute warming and acclimatisation, in the field, was tested in the seastar Odontaster validus collected in different years, seasons and locations within Antarctica. Finally, we tested the importance of oxygen limitation in controlling upper thermal limits. We found that four of 11 species studied were able to survive for more than 245 days (245-303 days) at higher than previously recorded temperatures, between 6 and 10 °C. Only survivors of the anemone Urticinopsis antarctica did not acclimate CTmax and there was no evidence of acclimatisation in O. validus. We found species-specific effects of mild hyperoxia (30% oxygen) on survival duration, which was extended (two species), not changed (four species) or reduced (one species), re-enforcing that oxygen limitation is not universal in dictating thermal survival thresholds. Thermal sensitivity is clearly the product of multiple ecological and physiological capacities, and this diversity of response needs further investigation and interpretation to improve our ability to predict future patterns of biodiversity.

The demise of large tropical brachiopods and the Mesozoic marine revolution.

Changes in predator-prey interactions are often implicated as drivers of major evolutionary change. A prominent example is the dramatic changes in shallow marine assemblages during the Mesozoic Marine Revolution (MMR) when major clades, including rhynchonelliform brachiopods, became restricted and less diverse. Currently, shallow-water temperate and polar brachiopods can be large, but in the tropics, they are small. By contrast, we demonstrate that throughout the Jurassic large brachiopods occurred in shallow sites, from polar to tropical latitudes, but are absent in later periods from tropical areas. These changes occurred in parallel in both major orders (Rhynchonellida and Terebratulida) and also independently within the two sub-ordinal lineages within the Terebratulida (terebratulinids and terebratellinids). Increases in both grazing and predation pressures associated with the MMR might account for this pattern. However, we note that many current environments support both large brachiopods and high densities of grazing species and suggest that the pattern fits more closely to the intensification of durophagous predation in shallow tropical waters.

Heptavalent O-Antigen Bioconjugate Vaccine Exhibiting Differential Functional Antibody Responses Against Diverse Klebsiella pneumoniae Isolates.

Klebsiella pneumoniae is the leading cause of neonatal sepsis and is increasingly difficult to treat owing to antibiotic resistance. Vaccination represents a tractable approach to combat this resistant bacterium; however, there is currently not a licensed vaccine. Surface polysaccharides, including O-antigens of lipopolysaccharide, have long been attractive candidates for vaccine inclusion. Herein we describe the generation of a bioconjugate vaccine targeting 7 predominant O-antigen subtypes in K. pneumoniae. Each bioconjugate was immunogenic in isolation, with limited cross-reactivity among subtypes. Vaccine-induced antibodies demonstrated varying degrees of binding to a wide variety of K. pneumoniae strains. Furthermore, serum from vaccinated mice induced complement-mediated killing of many of these strains. Finally, increased capsule interfered with the ability of O-antigen antibodies to bind and mediate killing of some K. pneumoniae strains. Taken together, these data indicate that this novel heptavalent O-antigen bioconjugate vaccine formulation exhibits limited efficacy against some, but not all, K. pneumoniae isolates.

Climate and human stressors on global penguin hotspots: Current assessments for future conservation.

As charismatic and iconic species, penguins can act as "ambassadors" or flagship species to promote the conservation of marine habitats in the Southern Hemisphere. Unfortunately, there is a lack of reliable, comprehensive, and systematic analysis aimed at compiling spatially explicit assessments of the multiple impacts that the world's 18 species of penguin are facing. We provide such an assessment by combining the available penguin occurrence information from Global Biodiversity Information Facility (>800,000 occurrences) with three main stressors: climate-driven environmental changes at sea, industrial fisheries, and human disturbances on land. Our analyses provide a quantitative assessment of how these impacts are unevenly distributed spatially within species' distribution ranges. Consequently, contrasting pressures are expected among species, and populations within species. The areas coinciding with the greatest impacts for penguins are the coast of Perú, the Patagonian Shelf, the Benguela upwelling region, and the Australian and New Zealand coasts. When weighting these potential stressors with species-specific vulnerabilities, Humboldt (Spheniscus humboldti), African (Spheniscus demersus), and Chinstrap penguin (Pygoscelis antarcticus) emerge as the species under the most pressure. Our approach explicitly differentiates between climate and human stressors, since the more achievable management of local anthropogenic stressors (e.g., fisheries and land-based threats) may provide a suitable means for facilitating cumulative impacts on penguins, especially where they may remain resilient to global processes such as climate change. Moreover, our study highlights some poorly represented species such as the Northern Rockhopper (Eudyptes moseleyi), Snares (Eudyptes robustus), and Erect-crested penguin (Eudyptes sclateri) that need internationally coordinated efforts for data acquisition and data sharing to understand their spatial distribution properly.

A horizon scan of global biological conservation issues for 2024.

We present the results of our 15th horizon scan of novel issues that could influence biological conservation in the future. From an initial list of 96 issues, our international panel of scientists and practitioners identified 15 that we consider important for societies worldwide to track and potentially respond to. Issues are novel within conservation or represent a substantial positive or negative step-change with global or regional extents. For example, new sources of hydrogen fuel and changes in deep-sea currents may have profound impacts on marine and terrestrial ecosystems. Technological advances that may be positive include benchtop DNA printers and the industrialisation of approaches that can create high-protein food from air, potentially reducing the pressure on land for food production.

Behavioural and physiological impacts of low salinity on the sea urchin Echinus esculentus.

Reduced seawater salinity as a result of freshwater input can exert a major influence on the ecophysiology of benthic marine invertebrates, such as echinoderms. While numerous experimental studies have explored the physiological and behavioural effects of short-term, acute exposure to low salinity in echinoids, surprisingly few have investigated the consequences of chronic exposure, or compared the two. In this study, the European sea urchin, Echinus esculentus, was exposed to low salinity over the short term (11‰, 16‰, 21‰, 26‰ and 31‰ for 24 h) and longer term (21, 26 and 31‰ for 25 days). Over the short term, oxygen consumption, activity coefficient and coelomic fluid osmolality were directly correlated with reduced salinity, with 100% survival at ≥21‰ and 0% at ≤16‰. Over the longer term at 21‰ (25 days), oxygen consumption was significantly higher, feeding was significantly reduced and activity coefficient values were significantly lower than at control salinity (31‰). At 26‰, all metrics were comparable to the control by the end of the experiment, suggesting acclimation. Furthermore, beneficial functional resistance (righting ability and metabolic capacity) to acute low salinity was observed at 26‰. Osmolality values were slightly hyperosmotic to the external seawater at all acclimation salinities, while coelomocyte composition and concentration were unaffected by chronic low salinity. Overall, E. esculentus demonstrate phenotypic plasticity that enables acclimation to reduced salinity around 26‰; however, 21‰ represents a lower acclimation threshold, potentially limiting its distribution in coastal areas prone to high freshwater input.

Resident microbes shape the vaginal epithelial glycan landscape.

Epithelial cells are covered in carbohydrates (glycans). This glycan coat or "glycocalyx" interfaces directly with microbes, providing a protective barrier against potential pathogens. Bacterial vaginosis (BV) is a condition associated with adverse health outcomes in which bacteria reside in direct proximity to the vaginal epithelium. Some of these bacteria, including Gardnerella, produce glycosyl hydrolase enzymes. However, glycans of the human vaginal epithelial surface have not been studied in detail. Here, we elucidate key characteristics of the "normal" vaginal epithelial glycan landscape and analyze the impact of resident microbes on the surface glycocalyx. In human BV, glycocalyx staining was visibly diminished in electron micrographs compared to controls. Biochemical and mass spectrometric analysis showed that, compared to normal vaginal epithelial cells, BV cells were depleted of sialylated N- and O-glycans, with underlying galactose residues exposed on the surface. Treatment of primary epithelial cells from BV-negative women with recombinant Gardnerella sialidases generated BV-like glycan phenotypes. Exposure of cultured VK2 vaginal epithelial cells to recombinant Gardnerella sialidase led to desialylation of glycans and induction of pathways regulating cell death, differentiation, and inflammatory responses. These data provide evidence that vaginal epithelial cells exhibit an altered glycan landscape in BV and suggest that BV-associated glycosidic enzymes may lead to changes in epithelial gene transcription that promote cell turnover and regulate responses toward the resident microbiome.

Ets1 and IL17RA cooperate to regulate autoimmune responses and skin immunity to Staphylococcus aureus.

Introduction: Ets1 is a lymphoid-enriched transcription factor that regulates B- and Tcell functions in development and disease. Mice that lack Ets1 (Ets1 KO) develop spontaneous autoimmune disease with high levels of autoantibodies. Naïve CD4 + T cells isolated from Ets1 KO mice differentiate more readily to Th17 cells that secrete IL-17, a cytokine implicated in autoimmune disease pathogenesis. To determine if increased IL-17 production contributes to the development of autoimmunity in Ets1 KO mice, we crossed Ets1 KO mice to mice lacking the IL-17 receptor A subunit (IL17RA KO) to generate double knockout (DKO) mice. Methods: In this study, the status of the immune system of DKO and control mice was assessed utilizing ELISA, ELISpot, immunofluorescent microscopy, and flow cytometric analysis of the spleen, lymph node, skin. The transcriptome of ventral neck skin was analyzed through RNA sequencing. S. aureus clearance kinetics in in exogenously infected mice was conducted using bioluminescent S. aureus and tracked using an IVIS imaging experimental scheme. Results: We found that the absence of IL17RA signaling did not prevent or ameliorate the autoimmune phenotype of Ets1 KO mice but rather that DKO animals exhibited worse symptoms with striking increases in activated B cells and secreted autoantibodies. This was correlated with a prominent increase in the numbers of T follicular helper (Tfh) cells. In addition to the autoimmune phenotype, DKO mice also showed signs of immunodeficiency and developed spontaneous skin lesions colonized by Staphylococcus xylosus. When DKO mice were experimentally infected with Staphylococcus aureus, they were unable to clear the bacteria, suggesting a general immunodeficiency to staphylococcal species. γδ T cells are important for the control of skin staphylococcal infections. We found that mice lacking Ets1 have a complete deficiency of the γδ T-cell subset dendritic epidermal T cells (DETCs), which are involved in skin woundhealing responses, but normal numbers of other skin γδ T cells. To determine if loss of DETC combined with impaired IL-17 signaling might promote susceptibility to staph infection, we depleted DETC from IL17RA KO mice and found that the combined loss of DETC and impaired IL-17 signaling leads to an impaired clearance of the infection. Conclusions: Our studies suggest that loss of IL-17 signaling can result in enhanced autoimmunity in Ets1 deficient autoimmune-prone mice. In addition, defects in wound healing, such as that caused by loss of DETC, can cooperate with impaired IL-17 responses to lead to increased susceptibility to skin staph infections.

Regulatory mechanisms to create healthier environments: planning appeals and hot food takeaways in England.

AIMS: To explore existing regulatory mechanisms to restrict hot food takeaway (HFT) outlets through further understanding processes at local and national levels. METHODS: The Planning Appeals Portal was utilised to identify recent HFT appeal cases across England between December 2016 and March 2020. Eight case study sites were identified using a purposive sampling technique and interviews carried out with 12 professionals involved in planning and health to explore perceptions of and including factors that may impact on the HFT appeal process. Additionally, documents applicable to each case were analysed and a survey completed by seven Local Authority (LA) health professionals. To confirm findings, interpretation meetings were conducted with participants and a wider group of planning and public health professionals, including a representative from the Planning Inspectorate. RESULTS: Eight case study sites were identified, and 12 interviews conducted. Participants perceived that LAs would be better able to work on HFT appeal cases if professionals had a good understanding of the planning process/the application of local planning policy and supplementary planning documents; adequate time and capacity to deal with appeals cases; access to accurate, robust, and up to date information; support and commitment from elected members and senior management; good lines of communication with local groups/communities interested in the appeal; information and resources that are accessible and easy to interpret across professional groups. CONCLUSIONS: Communication across professional groups appeared to be a key factor in successfully defending decisions. Understanding the impact of takeaway outlets on health and communities in the long term was also important. To create a more robust appeals case and facilitate responsiveness, professionals involved in an appeal should know where to locate current records and statistical data. The enthusiasm of staff and support from senior management/elected officials will play a significant role in driving these agendas forward.

An oral caspase inhibitor as monotherapy or with antibiotics eradicates MRSA skin infections in mice.

Staphylococcus aureus is the leading cause of skin and soft tissue infections. With the emergence of antibiotic-resistant bacteria, there is an unmet clinical need to develop immune-based therapies to treat skin infections. Previously, we have shown pan-caspase inhibition as a potential host-directed immunotherapy against community-acquired methicillin-resistant S aureus (CA-MRSA) and other bacterial skin infections. Here, we evaluated the role of irreversible pan-caspase inhibitor emricasan as a monotherapy and an adjunctive with a standard-of-care antibiotic, doxycycline, as potential host-directed immunotherapies against S. aureus skin infections in vivo. We used the established CA-MRSA strain USA300 on the dorsum of WT C57BL/6J mice and monitored lesion size and bacterial burden noninvasively, and longitudinally over 14 days with in vivo bioluminescence imaging (BLI). Mice in four groups placebo (0.5% carboxymethyl cellulose [CMC] solution), placebo plus doxycycline (100 mg/kg), emricasan (40 mg/kg) plus doxycycline, and emricasan only were treated orally twice daily by oral gavage for 7 days, starting at 4 h after injection of S aureus. When compared with placebo, all three groups, placebo plus doxycycline, emricasan plus doxycycline, and emricasan treated group, exhibited biological effect, with reduction of both the lesion size (*p = .0277, ****p < .0001, ****p < .0001, respectively) and bacterial burden (***p = .003, ****p < .0001, ****p < .0001, respectively). Importantly, the efficacy of emricasan against S. aureus was not due to direct antibacterial activity. Collectively, pan-caspase inhibitor emricasan and emricasan plus doxycycline reduced both the lesion size and bacterial burden in vivo, and emricasan is a potential host-directed immunotherapy against MRSA skin infections in a preclinical mouse model.

Management of abdominal wall hernias in patients with severe obesity.

Obesity is a risk factor for abdominal wall hernia development and hernia recurrence. The management of these two pathologies is complex and often entwined. Bariatric and ventral hernia surgery require careful consideration of physiologic and technical components for optimal outcomes. In this review, a multidisciplinary group of Society of American Gastrointestinal and Endoscopic Surgeons' bariatric and hernia surgeons present the various weight loss modalities available for the pre-operative optimization of patients with severe obesity and concurrent hernias. The group also details the technical aspects of managing abdominal wall defects during weight loss procedures and suggests the optimal timing of definitive hernia repair after bariatric surgery. Since level one evidence is not available on some of the topics covered by this review, expert opinion was implemented in some instances. Additional high-quality research in this area will allow for better recommendations and therefore treatment strategies for these complex patients.

Neutrophil-intrinsic TNF receptor signaling orchestrates host defense against Staphylococcus aureus.

Staphylococcus aureus is the leading cause of skin and soft tissue infections and is a major health burden due to the emergence of antibiotic-resistant strains. To address the unmet need of alternative treatments to antibiotics, a better understanding of the protective immune mechanisms against S. aureus skin infection is warranted. Here, we report that tumor necrosis factor (TNF) promoted protection against S. aureus in the skin, which was mediated by bone marrow-derived immune cells. Furthermore, neutrophil-intrinsic TNF receptor (TNFR) signaling directed immunity against S. aureus skin infections. Mechanistically, TNFR1 promoted neutrophil recruitment to the skin, whereas TNFR2 prevented systemic bacterial dissemination and directed neutrophil antimicrobial functions. Treatment with a TNFR2 agonist showed therapeutic efficacy against S. aureus and Pseudomonas aeruginosa skin infections, which involved increased neutrophil extracellular trap formation. Our findings revealed nonredundant roles for TNFR1 and TNFR2 in neutrophils for immunity against S. aureus and can be therapeutically targeted for protection against bacterial skin infections.

Capsular polysaccharide inhibits vaccine-induced O-antigen antibody binding and function across both classical and hypervirulent K2:O1 strains of Klebsiella pneumoniae.

Klebsiella pneumoniae presents as two circulating pathotypes: classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp). Classical isolates are considered urgent threats due to their antibiotic resistance profiles, while hvKp isolates have historically been antibiotic susceptible. Recently, however, increased rates of antibiotic resistance have been observed in both hvKp and cKp, further underscoring the need for preventive and effective immunotherapies. Two distinct surface polysaccharides have gained traction as vaccine candidates against K. pneumoniae: capsular polysaccharide and the O-antigen of lipopolysaccharide. While both targets have practical advantages and disadvantages, it remains unclear which of these antigens included in a vaccine would provide superior protection against matched K. pneumoniae strains. Here, we report the production of two bioconjugate vaccines, one targeting the K2 capsular serotype and the other targeting the O1 O-antigen. Using murine models, we investigated whether these vaccines induced specific antibody responses that recognize K2:O1 K. pneumoniae strains. While each vaccine was immunogenic in mice, both cKp and hvKp strains exhibited decreased O-antibody binding in the presence of capsule. Further, O1 antibodies demonstrated decreased killing in serum bactericidal assays with encapsulated strains, suggesting that the presence of K. pneumoniae capsule blocks O1-antibody binding and function. Finally, the K2 vaccine outperformed the O1 vaccine against both cKp and hvKp in two different murine infection models. These data suggest that capsule-based vaccines may be superior to O-antigen vaccines for targeting hvKp and some cKp strains, due to capsule blocking the O-antigen.