Anti-CfaE nanobodies provide broad cross-protection against major pathogenic enterotoxigenic Escherichia coli strains, with implications for vaccine design

Enterotoxigenic Escherichia coli (ETEC) is estimated to cause approximately 380,000 deaths annually during sporadic or epidemic outbreaks worldwide. Development of vaccines against ETEC is very challenging due to the vast heterogeneity of the ETEC strains. An effective vaccines would have to be multicomponent to provide coverage of over ten ETEC strains with genetic variabilities. There is currently no vaccine licensed to prevent ETEC. Nanobodies are successful new biologics in treating mucosal infectious disease as they recognize conserved epitopes on hypervariable pathogens. Cocktails consisting of multiple nanobodies could provide even broader epitope coverage at a lower cost compared to monoclonal antibodies. Identification of conserved epitopes by nanobodies can also assist reverse engineering of an effective vaccine against ETEC. By screening nanobodies from immunized llamas and a naive yeast display library against adhesins of colonization factors, we identified single nanobodies that show cross-protective potency against eleven major pathogenic ETEC strains in vitro. Oral administration of nanobodies led to a significant reduction of bacterial colonization in animals. Moreover, nanobody-IgA fusion showed extended inhibitory activity in mouse colonization compared to commercial hyperimmune bovine colostrum product used for prevention of ETEC-induced diarrhea. Structural analysis revealed that nanobodies recognized a highly-conserved epitope within the putative receptor binding region of ETEC adhesins. Our findings support further rational design of a pan-ETEC vaccine to elicit robust immune responses targeting this conserved epitope

Strukturrevision einer weit verbreiteten marinen Sulfonolipidklasse basierend auf deren Isolierung und Totalsynthese

Bakterien der marinen Roseobacter-Gruppe spielen eine wichtige Rolle in globalen biogeochemischen Prozessen. Prominente Vetreter dieser Gruppe produzieren schwefelhaltige Aminolipide (SAL), die für die Bildung von Biofilmen und die Besiedlung von Meeresoberflächen von entscheidender Bedeutung sind. Obwohl Genome Mining-Ansätze und massenspektrometrische Studien homotaurinhaltige Strukturen für eine Gruppe von SALs postulierten, blieben deren relative und absolute Strukturen bisher unbekannt, was biochemische und funktionelle Untersuchungen behinderte. In dieser Studie konnten wir die absoluten Strukturen durch eine Kombination von analytischen Techniken, Isolierungs- und Abbauexperimenten sowie Totalsynthese bestimmen. Im Gegensatz zu vorherigen Strukturvorschlägen sind die hier untersuchten Aminolipide durch eine ungewöhnliche N,O-acylierte Cysteinolsäure Kopfgruppe gekennzeichnet, weshalb wir die Substanzklasse Cysteinolide genannt haben. Durch gezielte Netzwerk-basierende metabolomische Studien konnten wir zudem die Verteilung und strukturelle Vielfalt von Cysteinoliden in verschiedenee Vertretern der bakteriellen Roseobacter-Gruppe kartieren. Insgesamt konnten in dieser Studie 14 verschiedene Aminolipide, einschließlich der in dieser Studie isolierten Cysteinolide, synthetisiert werden. Der Vergleich der erhaltenen analytischen Daten ermöglichte tiefergehende strukturelle Einblicke in die Charakteristika diese Substanzgruppe, welche für Studien zum bakteriellen Sulfonolipid-Stoffwechsel und zu biogeochemischen Nährstoffkreislauf in den Ozeanen von großer Bedeutung sein werden

Using Rapid-Cycle Change to Improve COVID-19 Vaccination Strategy in Primary Care

During the COVID-19 pandemic, misinformation and distrust exacerbated disparities in vaccination rates by race and ethnicity throughout the United States. Primary care, public health systems, and community health centers have shifted their vaccination outreach strategies toward these disparate, unvaccinated populations. To support primary care, we developed the SAVE Sprint model for implementing rapid-cycle change to improve vaccination rates by overcoming community outreach barriers and workforce limitations. Participants were recruited for the 10-week SAVE Sprint program through partnerships with the National Association of Community Health Centers (NACHC) and the Resilient American Communities (RAC) Initiative. The majority of the participants were from community health centers. Data were evaluated during the program through progress reports and surveys, and interviews conducted three months post-intervention were recorded, coded, and analyzed. The SAVE Sprint model of rapid-cycle change exceeded participants’ expectations and led to improvements in patient education and vaccination among their vulnerable populations. Participants reported building new skills and identifying strategies for targeting specific populations during a public health emergency. However, participants reported that planning for rapid-pace change and trust-building with community partners prior to a health care crisis is preferable and would make navigating an emergency easier

Pollution swapping in arable agricultural systems.

Pollution swapping occurs when a mitigation option introduced to reduce one pollutant results in an increase in a different pollutant. Although the concept of pollution swapping is widely understood, it has received little attention in research and policy design. This study investigated diffuse pollution mitigation options applied in combinable crop systems. They are cover crops, residue management, no-tillage, riparian buffer zones, contour grass strips, and constructed wetlands. A wide range of water and atmospheric pollutants were considered, including nitrogen, phosphorus, carbon, and sulfur. It is clear from this investigation that there is no single mitigation option that will reduce all pollutants

Structure Revision of a Widespread Marine Sulfonolipid Class Based on Isolation and Total Synthesis

The cosmopolitan marine Roseobacter clade is of global biogeochemical importance. Members of this clade produce sulfur-containing amino lipids (SALs) of importance for biofilm formation and marine surface colonization processes. Despite their physiological importance and abundance, SALs have only been explored through genomic mining approaches and lipidomic studies based on mass spectrometry, which left the relative and absolute structures of SALs unresolved hindering progress in biochemical and functional investigations. Here, we report the structural revision of a new group of SALs, which we named cysteinolides, using a combination of analytical techniques, isolation and degradation experiments and total synthetic efforts. Contrary to the previously proposed homotaurine-based structures, cysteinolides are composed of an N,O-acylated cysteinolic acid-containing head group carrying various different (α‑hydroxy) carboxylic acids. We performed the first validated targeted-network based analysis, which allowed us to map the distribution and structural diversity of cysteinolides across bacterial lineages. Beyond offering structural insights, our research provides SAL standards and validated analytical data. This information holds significance for forthcoming investigations into bacterial sulfonolipid metabolism and biogeochemical nutrient cycling within marine environments.</p