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The positive response of wetland methane (CH4) emissions to climate change is an important yet uncertain Earth-system feedback that amplifies atmospheric CH4 concentrations. Here, using a wetland model, we report intensified wetland CH4 emissions during 2000–2021, corresponding with 2020 and 2021 being exceptional years of growth. Our results highlight the need for sustained monitoring and observations of global wetland CH4 fluxes to document emerging trends, variability and underlying drivers.

The global carbon cycle is experiencing continued perturbations via increases in atmospheric carbon concentrations, which are partly reduced by terrestrial biosphere and ocean carbon uptake. Greenhouse gas satellites have been shown to be useful in retrieving atmospheric carbon concentrations and observing surface and atmospheric CO2 seasonal-to-interannual variations. However, limited attention has been placed on using satellite column CO2 retrievals to evaluate surface CO2 fluxes from the terrestrial biosphere without advanced inversion models at low latency. Such applications could be useful to monitor, in near real time, biosphere carbon fluxes during climatic anomalies like drought, heatwaves, and floods, before more complex terrestrial biosphere model outputs and/or advanced inversion modelling estimates become available. Here, we explore the ability of Orbiting Carbon Observatory-2 (OCO-2) column-averaged dry air CO2 (XCO2) retrievals to directly detect and estimate terrestrial biosphere CO2 flux anomalies using a simple mass-balance approach. An initial global analysis of surface–atmospheric CO2 coupling and transport conditions reveals that the western US, among a handful of other regions, is a feasible candidate for using XCO2 for detecting terrestrial biosphere CO2 flux anomalies. Using the CarbonTracker model reanalysis as a test bed, we first demonstrate that a well-established mass-balance approach can estimate monthly surface CO2 flux anomalies from XCO2 enhancements in the western United States. The method is optimal when the study domain is spatially extensive enough to account for atmospheric mixing and has favorable advection conditions with contributions primarily from one background region. We find that errors in individual soundings reduce the ability of OCO-2 XCO2 to estimate more frequent, smaller surface CO2 flux anomalies. However, we find that OCO-2 XCO2 can often detect and estimate large surface flux anomalies that leave an imprint on the atmospheric CO2 concentration anomalies beyond the retrieval error/uncertainty associated with the observations. OCO-2 can thus be useful for low-latency monitoring of the monthly timing and magnitude of extreme regional terrestrial biosphere carbon anomalies.

Vegetation cover creates competing effects on land surface temperature: it typically cools through enhancing energy dissipation and warms via decreasing surface albedo. Global vegetation has been previously found to overall net cool land surfaces with cooling contributions from temperate and tropical vegetation and warming contributions from boreal vegetation. Recent studies suggest that dryland vegetation across the tropics strongly contributes to this global net cooling feedback. However, observation-based vegetation-temperature interaction studies have been limited in the tropics, especially in their widespread drylands. Theoretical considerations also call into question the ability of dryland vegetation to strongly cool the surface under low water availability. Here, we use satellite observations to investigate how tropical vegetation cover influences the surface energy balance. We find that while increased vegetation cover would impart net cooling feedbacks across the tropics, net vegetal cooling effects are subdued in drylands. Using observations, we determine that dryland plants have less ability to cool the surface due to their cooling pathways being reduced by aridity, overall less efficient dissipation of turbulent energy, and their tendency to strongly increase solar radiation absorption. As a result, while proportional greening across the tropics would create an overall biophysical cooling feedback, dryland tropical vegetation reduces the overall tropical surface cooling magnitude by at least 14%, instead of enhancing cooling as suggested by previous global studies.

Capsular polysaccharides (CPSs), with which most pathogenic bacterial surfaces are decorated, have been used as the main components of glycoconjugate vaccines against bacterial diseases in clinical practice worldwide. Pneumococcal conjugate vaccines (PCVs) are administered globally to prevent invasive pneumococcal disease (IPD). While PCVs have played important roles in controlling IPD in all age groups, their empirical, and labor-intensive chemical conjugation yield poorly characterized, heterogeneous, and variably immunogenic vaccines, with poor immune responses in high-risk populations such as the elderly and patients with weak immune systems. We previously developed a method that bypasses the dependency of chemical conjugation and instead exploits prokaryotic glycosylation systems to produce pneumococcal conjugate vaccines. The bioconjugation platform relies on a conjugating enzyme to transfer a bacterial polysaccharide to an engineered carrier protein all within the lab safe bacterium E. coli. In these studies, we demonstrate that a serotype 8 pneumococcal bioconjugate vaccine is highly immunogenic and elicits functionally protective anti-serotype 8 antibody responses. Specifically, using multiple models we show that mice immunized with multiple doses of a serotype 8 bioconjugate vaccine elicit antibody responses that mediate opsonophagocytic killing, protect mice from systemic infection, and decrease the ability of serotype 8 pneumococci to colonize the nasopharynx and disseminate. Collectively, these studies demonstrate the utility of bioconjugation to produce efficacious pneumococcal conjugate vaccines.

Background Two SARS-CoV-2 waves in Israel ended while a substantial number of individuals remained unvaccinated or partially vaccinated. The indirect protective effect of the first BNT162b2 vaccination campaign in Israel was evaluated between 22 December 2020 and 18 May 2021. Methods The daily percentage of new polymerase chain reaction (PCR)–confirmed SARS-CoV-2 cases among unvaccinated individuals was analyzed for trends. Major shifts were identified using piecewise linear regression analysis. At these shifts, the percentage of naturally vaccinated (past SARS-CoV-2 cases) and the percentage of actively vaccinated (by inoculation) individuals were weighted and summed to determine the percentage of natural and active vaccination (NAV). Results A first decline among unvaccinated individuals occurred during a lockdown period, when the percentage of NAV was 8.16%. The major decline occurred after the end of the lockdown when the percentage of NAV reached 52.05%. SARS-CoV-2 cases ultimately declined among unvaccinated individuals when the percentage of NAV reached 63.55%. During the study period, the Alpha variant was prevalent and the use of nonpharmaceutical interventions, including social distancing, existed to varying degrees. Conclusions The vaccination campaign played a major role in the decline of SARS-CoV-2 infection among unvaccinated individuals, leading to the end of the first 2021 SARS-CoV-2 wave (Alpha variant) in Israel. Infection in unvaccinated individuals stopped when two-thirds of the population were naturally or actively vaccinated. Any change in characteristics of the virus or the population can lead to a new outbreak.

The indium phosphide (InP) 130 nm double-heterojunction bipolar transistor (DHBT) offers milliwatts of output power and high signal amplification in the lower end of the terahertz frequency band when the transistor is used in a common-base configuration. Instrumentation can directly benefit from this technology by enabling the development of novel broadband sources or synthesizers that rely on our ability to amplify the signal over enormous bandwidths. However, the design of high gain and stable amplifiers presents many obstacles and limitations as we increase the bandwidth and the carrier frequency. Here we show that adding a series resistor at the collector terminal of the common-base transistor prevents instabilities in the terahertz monolithic integrated circuit (TMIC) amplifier and increases its fractional bandwidth. Adopting this technique, we report a state-of-the-art broadband common-base amplifier that exhibits a minimum small-signal gain of 18.9 dB from 325 GHz to 477 GHz. This amplifier presents the highest fractional bandwidth and gain above 300 GHz. Our work demonstrates the feasibility of high-performance amplifiers that address the need of future terahertz electronic systems.

Multidrug-resistant Acinetobacter baumannii infections are an urgent clinical problem and can cause difficult-to-treat nosocomial infections. During such infections, like catheter-associated urinary tract infections (CAUTI), A. baumannii rely on adhesive, extracellular fibers, called chaperone-usher pathway (CUP) pili for critical binding interactions. The A. baumannii uropathogenic strain, UPAB1, and the pan-European subclone II isolate, ACICU, use the CUP pili Abp1 and Abp2 (previously termed Cup and Prp, respectively) in tandem to establish CAUTIs, specifically to facilitate bacterial adherence and biofilm formation on the implanted catheter. Abp1 and Abp2 pili are tipped with two domain tip adhesins, Abp1D and Abp2D, respectively. We discovered that both adhesins bind fibrinogen, a critical host wound response protein that is released into the bladder upon catheterization and is subsequently deposited on the catheter. The crystal structures of the Abp1D and Abp2D receptor-binding domains were determined and revealed that they both contain a large, distally oriented pocket, which mediates binding to fibrinogen and other glycoproteins. Genetic, biochemical, and biophysical studies revealed that interactions with host proteins are governed by several critical residues in and along the edge of the binding pocket, one of which regulates the structural stability of an anterior loop motif. K34, located outside of the pocket but interacting with the anterior loop, also regulates the binding affinity of the protein. This study illuminates the mechanistic basis of the critical fibrinogen-coated catheter colonization step in A. baumannii CAUTI pathogenesis.

The antibiotic-resistant bacterium Acinetobacter baumannii is a leading cause of hospital-associated infections. Despite surveillance and infection control efforts, new A. baumannii strains are regularly isolated from health care facilities worldwide. In a mouse model of urinary tract infection, we found that mice infected with A. baumannii displayed high bacterial burdens in urine for several weeks. Two months after the resolution of A. baumannii infection, inserting a catheter into the bladder of mice with resolved infection led to the resurgence of a same-strain urinary tract infection in ~53% of the mice within 24 hours. We identified intracellular A. baumannii bacteria in the bladder epithelial cells of mice with resolved infection, which we propose could act as a host reservoir that was activated upon insertion of a catheter, leading to a resurgent secondary infection.

Background Limited data exist on the long-term consequences of bloodstream infections (BSI). We examined incidence, 1-year mortality, and years of potential life lost (YPLL) following BSI by eight sentinel bacteria in adults. We also estimated the relative contribution of hospital-onset BSI (HO-BSI) and of antibiotic-resistant BSI to the burden of BSI. Methods We used data from Israel's national BSI surveillance system (covering E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, S. pneumoniae, S. aureus, E. faecalis and E. faecium, comprising 70% of all BSI) and the national death registry. Adults with BSI between 1/1/2018 and 31/12/2019 were included. The outcomes were all-cause 30-day and 1-year mortality. We constructed Kaplan-Meier curves and used the log-rank test to compare survival between age groups. We calculated the age-standardized mortality rate and YPLL using the Global Burden of Disease reference population and life expectancy tables. Results A total of 25,376 BSI occurred over 2 years in the adult Israeli population (mean adult population: 6,068,580). Drug-resistant BSI comprised 32% of all events (41.1% of HO-BSI). The annual BSI incidence was 209 per 100,000 population. The case fatality rate (CFR) was 25.6% at 30 days and 46.4% at 1 year. The 1-year CFR was higher among males than females (RR=1.17, 95% CI 1.14–1.20) and it increased with age (OR=1.37 per decade, 95% CI 1.36–1.39). In all age groups survival continued to decline up to 1 year (Figure). For the outcome of 1-year mortality, the annual age-standardized mortality rate and YPLL per 100,000 population following BSI were 48.6 and 1002.2, respectively. For comparison, the global mortality rate and YPLL from ischemic stroke are 36.6 and 521.8 per 100,000, respectively. HO-BSI represented 27.4% of BSI but contributed to 33.9% of deaths and 39.9% of YPLL. HO-BSI by drug-resistant bacteria represented 11.3% of BSI, 14.8% of deaths, and 17.4% of YPLL. Conclusion BSI have grave long-term consequences: nearly 50% of affected adult patients died within 1 year. The burden of BSI is higher than that of ischemic stroke. HO-BSI and drug-resistant BSI contribute disproportionately to BSI mortality and YPLL. Attention and resources should be directed to prevention of BSI, as well as to advances in early diagnosis and better treatment. Disclosures Yehuda Carmeli, MD, Allecra Therapeutics: Advisor/Consultant|MSD: Advisor/Consultant|Nabriva: Advisor/Consultant|Pfizer: Advisor/Consultant|Qpex Pharmaceuticals: Advisor/Consultant|Roche: Advisor/Consultant|Shinogi: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant.

Secretion of cellular components across the plasma membrane is an essential process that enables organisms to interact with their environments. Production of extracellular vesicles in bacteria is a well-documented but poorly understood process. Outer membrane vesicles (OMVs) are produced in gram-negative bacteria by blebbing of the outer membrane. In addition to their roles in pathogenesis, cell-to-cell communication, and stress responses, OMVs play important roles in immunomodulation and the establishment and balance of the gut microbiota. In this review, we discuss the multiple roles of OMVs and the current knowledge of OMV biogenesis. We also discuss the growing and promising biotechnological applications of OMV.

Limited data exist on long-term consequences of bloodstream infections (BSIs). We aimed to examine incidence, 1-year mortality, and years of potential life lost (YPLL) following BSI. We estimated the relative contribution of hospital-onset BSI (HO-BSI) and antibiotic-resistant BSI to incidence, mortality and YPLL.We used data from Israel's national BSI surveillance system (covering eight sentinel bacteria, comprising 70% of all BSIs) and the national death registry. Adults with BSI between January 2018 and December 2019 were included. The outcomes were all-cause 30-day and 1-year mortality, with no adjustment for co-morbidities. We calculated the age-standardized mortality rate and YPLL using the Global Burden of Disease reference population and life expectancy tables.In total, 25,376 BSIs occurred over 2 years (mean adult population: 6,068,580). The annual incidence was 209·1 BSIs (95% CI 206·5-211·7) per 100,000 population. The case fatality rate was 25·6% (95% CI 25·0-26·2) at 30 days and 46·4% (95% CI 45·5-47·2) at 1 year. The hazard of death increased by 30% for each decade of age (HR=1·3 [95% CI 1·2-1·3]). The annual age-standardized mortality rate and YPLL per 100,000 were 50·8 (95% CI 49·7-51·9) and 1,012·6 (95% CI 986·9-1,038·3), respectively. HO-BSI (6,962 events) represented 27·4% (95% CI 26·9-28·0) of BSIs, 33·9% (95% CI 32·6-35·0) of deaths and 39·9% (95% CI 39·5-40·2) of YPLL. HO-BSI by drug-resistant bacteria (3,072 events) represented 12·1% (95% CI 11·7-12·5) of BSIs, 15·6% (95% CI 14·7-16·5) of deaths, and 18·4% (95% CI 18·1-18·7) of YPLL.One-year mortality following BSI is high. The burden of BSI is similar to that of ischemic stroke. HO-BSI and drug-resistant BSI contribute disproportionately to BSI mortality and YPLL.None.

The global carbon cycle is experiencing continued perturbations via increases in atmospheric carbon concentrations. Greenhouse gas satellites that are designed to retrieve atmospheric carbon concentrations can help observe seasonal to interannual variations and sources of carbon dioxide. Recent work has shown that these satellites are further applicable beyond their design specifications for directly identifying and quantifying surface emissions at various spatial and temporal scales. For example, simple model translations of atmospheric carbon concentrations to surface carbon exchanges have been used to rapidly estimate surface methane fluxes from satellite observations of methane in the atmosphere. However, less attention has been placed on using satellite column CO2 retrievals to evaluate surface CO2 fluxes from the terrestrial biosphere at shorter timescales without more complex inversion models. Such applications could be useful to monitor, in near-real time, biosphere carbon fluxes during climatic anomalies like drought, heatwaves, and floods, before more complex terrestrial biosphere model outputs become available. Here, we explore the ability of Orbiting Carbon Observatory-2 (OCO-2) satellite retrievals of column-averaged dry air CO2 (XCO2) to directly detect and estimate terrestrial biosphere CO2 flux anomalies using a simple mass balance approach. Using a regional model simulation (CarbonTracker reanalysis) as a testbed, we first demonstrate that a previously developed, simple model can rapidly estimate monthly surface CO2 flux anomalies from atmospheric XCO2 estimates in the Western United States. The method is optimal when the chosen study domain is spatially extensive enough to account for atmospheric mixing and has favorable wind conditions with incoming wind contributions primarily from the same region. While errors in individual satellite measurements partially reduce the ability of OCO-2 satellite XCO2 to estimate more frequent, smaller surface CO2 flux anomalies, we find that OCO-2 XCO2 can often detect and estimate larger surface flux anomalies that are due to droughts and heatwaves. OCO-2 is thus useful for near real time monitoring of the monthly ecosystem behavior and health. Any noise reduction in forthcoming greenhouse gas satellites and/or the existence of large surface carbon anomalies will likely enhance the ability to rapidly estimate surface fluxes at shorter timescales scales.

Background The incidence of Escherichia coli bloodstream infections (BSI) is high and increasing. We aimed to describe the effect of season and temperature on the incidence of E. coli BSI and antibiotic-resistant E. coli BSI and to determine differences by place of BSI onset. Methods All E. coli BSI in adult Israeli residents between January 1, 2018 and December 19, 2019 were included. We used the national database of mandatory BSI reports and outdoor temperature data. Monthly incidence and resistance were studied using multivariable negative binomial regressions with season (July–October vs. other) and temperature as covariates. Results We included 10,583 events, 9012 (85%) community onset (CO) and 1571 (15%) hospital onset (HO). For CO events, for each average monthly temperature increase of 5.5 °C, the monthly number of events increased by 6.2% (95% CI 1.6–11.1%, p = 0.008) and the monthly number of multidrug-resistant events increased by 4.9% (95% CI 0.3–9.7%, p = 0.04). The effect of season was not significant. For HO events, incidence of BSI and resistant BSI were not associated with temperature or season. Conclusion Temperature increases the incidence of CO E. coli BSI and CO antibiotic-resistant E. coli BSI. Global warming threatens to increase the incidence of E. coli BSI.

Acinetobacter baumannii causes a wide range of infections that are difficult to treat due to increasing rates of multidrug resistance; however, the mechanisms that this pathogen uses to respond to stress are poorly understood. Here, we describe a new mechanism of stress signaling in Acinetobacter that is mediated by the metabolite phenylacetic acid (PAA).

Acinetobacter baumannii is an opportunistic pathogen of growing concern, as isolates are commonly multidrug resistant. While A. baumannii is most frequently associated with pulmonary infections, a significant proportion of clinical isolates come from urinary sources, highlighting its uropathogenic potential. The type IIsecretion system (T2SS) of commonly used model Acinetobacter strains is important for virulence in various animal models, but the potential role of the T2SS in urinary tract infection (UTI) remains unknown. Herein, we used a catheter-associated UTI (CAUTI) model to demonstrate that a modern urinary isolate, UPAB1, requires the T2SS for full virulence. A proteomic screen to identify putative UPAB1 T2SS effectors revealed an uncharacterized lipoprotein with structural similarity to the intimin-invasin family, which serve as type Vsecretion system (T5SS) adhesins required for the pathogenesis of several bacteria. This protein, designated InvL, lacked the β-barrel domain associated with T5SSs, but was confirmed to require the T2SS for both surface localization and secretion. This makes InvL the first identified T2SS effector belonging to the intimin-invasin family. InvL was confirmed to be an adhesin, as the protein bound to extracellular matrix components and mediated adhesion to urinary tract cell lines in vitro. Additionally, the invL mutant was attenuated in the CAUTI model, indicating a role in Acinetobacter uropathogenesis. Finally, bioinformatic analyses revealed that InvL is present in nearly all clinical isolates belonging to international clone 2, a lineage of significant clinical importance. In all, we conclude that the T2SS substrate InvL is an adhesin required for A. baumannii uropathogenesis.IMPORTANCEWhile pathogenic Acinetobacter can cause various infections, we recently found that 20% of clinical isolates come from urinary sources. Despite the clinical relevance of Acinetobacter as a uropathogen, few virulence factors involved in urinary tract colonization have been defined. Herein, we identify a novel type II secretion system effector, InvL, which is required for full uropathogenesis by a modern urinary isolate. Though InvL has predicted structural similarity to the intimin-invasin family of autotransporter adhesins, InvL is predicted to be anchored to the membrane as a lipoprotein. Similar to other invasin homologs however, we demonstrate that InvL is a bona fide adhesin capable of binding extracellular matrix components and mediating adhesion to urinary tract cell lines. In all, this work establishes InvL as an adhesin important for Acinetobacter’s urinary tract virulence, and represents the first report of a type II secretion system effector belonging to the intimin-invasin family.

Variation in canopy water content (CWC) that can be detected from microwave remote sensing of vegetation optical depth (VOD) has been proposed as an important measure of vegetation water stress. However, the contribution of leaf surface water (LWs ), arising from dew formation and rainfall interception, to CWC is largely unknown, particularly in tropical forests and other high-humidity ecosystems. We compared VOD data from the Advanced Microwave Scanning Radiometer for the Earth Observing System (AMSR-E) and CWC predicted by a plant hydrodynamics model at four tropical sites in Brazil spanning a rainfall gradient. We assessed how LWs influenced the relationship between VOD and CWC. The analysis indicates that while CWC is strongly correlated with VOD (R2 = 0.62 across all sites), LWs accounts for 61-76% of the diurnal variation in CWC despite being < 10% of CWC. Ignoring LWs weakens the near-linear relationship between CWC and VOD and reduces the consistency in diurnal variation. The contribution of LWs to CWC variation, however, decreases at longer, seasonal to inter-annual, time scales. Our results demonstrate that diurnal patterns of dew formation and rainfall interception can be an important driver of diurnal variation in CWC and VOD over tropical ecosystems and therefore should be accounted for when inferring plant diurnal water stress from VOD measurements.

The transition of evapotranspiration between energy- and water-limitation regimes also denotes a nonlinear change in surface water and energy coupling strength. The regime transitions are primarily dominated by available moisture in the soil, although other micro-meteorological factors also play a role. Remotely sensed soil moisture is frequently used for detecting evapotranspiration regime transitions during inter storm dry downs. However, its sampling depth does not include the entire soil profile, over which water uptake is dominated by plant root distribution. We use flux tower, surface (

Understanding and reducing the uncertainties in the inversion of the first-order radiative transfer models at the L-band are important for the improved spaceborne retrievals of soil moisture (SM) and vegetation optical depth (VOD) over dense canopy. This article quantifies and compares the sensitivity of dual-channel inversion of the two-stream (2S) and $\tau $ – $\omega $ models and proposes a new inversion approach for simultaneous retrievals of SM, VOD, and vegetation-scattering albedo ( $\omega $ ) from a single satellite overpass. In particular, the inversion algorithm incorporates the information of the nearby spatial observations, assuming that the values of VOD and $\omega $ remain locally invariant, and constrains its solutions to high-resolution a priori physical/climatological knowledge of the retrieval variables. The results demonstrate that the uncertainty in the inversion of 2S model is slightly higher than the $\tau $ – $\omega $ model under noisy observations and remains homoscedastic for SM and $\omega $ , while grows heteroscedastically for higher VOD values due to the shape of the cost function. The results are validated using the SMAP data, the dense Mesonet SM network, the in situ measurements from the International SM Network (ISMN), and the derived VOD from the Moderate Resolution Imaging Spectroradiometer (MODIS)-normalized difference vegetation index (NDVI) over the state of Oklahoma in the United States. It is shown that the new approach can recover simultaneously high-resolution features of SM, VOD, and $\omega $ only from a single Soil Moisture Active Passive (SMAP) overpass, where the unbiased root-mean-squared error (ubRMSE) of SM and VOD is reduced by 30% and 70%, respectively, when compared with an unconstrained time-windowed inversion approach.

Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. Although rare in bacteria, sphingolipids are produced by members of the phylum “ Bacteroidetes ,” human gut commensals. Here, we determined that OMVs carry sphingolipids and other lipids of known signaling function. Our results demonstrate that the BT1522–1526 operon is required for IPC biosynthesis in B. thetaiotaomicron .

Acinetobacter baumannii is emerging as a multidrug-resistant (MDR) nosocomial pathogen of increasing threat to human health worldwide. The recent MDR urinary isolate UPAB1 carries the plasmid pAB5, a member of a family of large conjugative plasmids (LCP). LCP encode several antibiotic resistance genes and repress the type VI secretion system (T6SS) to enable their dissemination, employing two TetR transcriptional regulators. Furthermore, pAB5 controls the expression of additional chromosomally encoded genes, impacting UPAB1 virulence. Here we show that a pAB5-encoded H-NS transcriptional regulator represses the synthesis of the exopolysaccharide PNAG and the expression of a previously uncharacterized three-gene cluster that encodes a protein belonging to the CsgG/HfaB family. Members of this protein family are involved in amyloid or polysaccharide formation in other species. Deletion of the CsgG homolog abrogated PNAG production and Cup pili formation, resulting in a subsequent reduction in biofilm formation. Although this gene cluster is widely distributed in Gram-negative bacteria, it remains largely uninvestigated. Our results illustrate the complex cross-talks that take place between plasmids and the chromosomes of their bacterial host, which in this case can contribute to the pathogenesis of Acinetobacter.IMPORTANCEThe opportunistic human pathogen Acinetobacter baumannii displays the highest reported rates of multidrug resistance among Gram-negative pathogens. Many A. baumannii strains carry large conjugative plasmids like pAB5. In recent years, we have witnessed an increase in knowledge about the regulatory cross-talks between plasmids and bacterial chromosomes. Here we show that pAB5 controls the composition of the bacterial extracellular matrix, resulting in a drastic reduction in biofilm formation. The association between biofilm formation, virulence, and antibiotic resistance is well-documented. Therefore, understanding the factors involved in the regulation of biofilm formation in Acinetobacter has remarkable therapeutic potential.

Group B Streptococcus (GBS) is a leading cause of neonatal infections and invasive diseases in nonpregnant adults worldwide. Developing a protective conjugate vaccine targeting the capsule of GBS has been pursued for more than 30 years; however, it has yet to yield a licensed product. In this study, we present a novel bioconjugation platform for producing a prototype multivalent GBS conjugate vaccine and its subsequent analytical and immunological characterizations. Using a glycoengineering strategy, we generated strains of Escherichia coli that recombinantly express the type Ia, type Ib, and type III GBS capsular polysaccharides. We then combined the type Ia-, Ib-, and III-capsule-expressing E. coli strains with an engineered Pseudomonas aeruginosa exotoxin A (EPA) carrier protein and the PglS oligosaccharyltransferase. Coexpression of a GBS capsule, the engineered EPA protein, and PglS enabled the covalent attachment of the target GBS capsule to an engineered serine residue on EPA, all within the periplasm of E. coli. GBS bioconjugates were purified, analytically characterized, and evaluated for immunogenicity and functional antibody responses. This proof-of-concept study signifies the first step in the development of a next-generation multivalent GBS bioconjugate vaccine, which was validated by the production of conjugates that are able to elicit functional antibodies directed against the GBS capsule.

The question of the role of prenatal sex hormones in human psychosexual differentiation originated in the clinical context of intersexuality and its management problems. Sex hormones affect the size of certain cell clusters, shapes of dendritic trees, and types of synapses; such sex-dimorphic structures have been localized in several areas of the brain, particularly in the hypothalamus and the preoptic area. The use of sex hormones in the treatment of problem pregnancies was first introduced in the 1940s, after it had become known that successful initiation as well as maintenance of pregnancy depended, on hormones produced by the mother as well as by the feto-placental unit. Thus, the available observations suggest that prenatal sex hormones contribute to the development of behavioral differences between the sexes in general as it has been demonstrated in animal research. The tendencies are likely to facilitate or inhibit certain behavior effects of the sex-typing pressures that the developing individual encounters in the social environment.

Acinetobacter baumannii is emerging as a multidrug-resistant (MDR) nosocomial pathogen of increasing threat to human health worldwide. The recent MDR urinary isolate UPAB1 carries the plasmid pAB5, a member of a family of large conjugative plasmids (LCPs). LCPs encode several antibiotic resistance genes and repress the type VI secretion system (T6SS) to enable their dissemination, employing two TetR transcriptional regulators. Furthermore, pAB5 controls the expression of additional chromosomally encoded genes, impacting UPAB1 virulence. Here, we show that a pAB5-encoded H-NS transcriptional regulator represses the synthesis of the exopolysaccharide PNAG and the expression of a previously uncharacterized three-gene cluster that encodes a protein belonging to the CsgG/HfaB family. Members of this protein family are involved in amyloid or polysaccharide formation in other species. Deletion of the CsgG homolog abrogated PNAG production and chaperone-usher pathway (CUP) pilus formation, resulting in a subsequent reduction in biofilm formation. Although this gene cluster is widely distributed in Gram-negative bacteria, it remains largely uninvestigated. Our results illustrate the complex cross-talks that take place between plasmids and the chromosomes of their bacterial host, which in this case can contribute to the pathogenesis of Acinetobacter. IMPORTANCE The opportunistic human pathogen Acinetobacter baumannii displays the highest reported rates of multidrug resistance among Gram-negative pathogens. Many A. baumannii strains carry large conjugative plasmids like pAB5. In recent years, we have witnessed an increase in knowledge about the regulatory cross-talks between plasmids and bacterial chromosomes. Here, we show that pAB5 controls the composition of the bacterial extracellular matrix, resulting in a drastic reduction in biofilm formation. The association between biofilm formation, virulence, and antibiotic resistance is well documented. Therefore, understanding the factors involved in the regulation of biofilm formation in Acinetobacter has remarkable therapeutic potential.

A retrieval methodology for forest water potential from ground-based L-band radiometry is proposed. It contains the estimation of the gravimetric and the relative water content of a forest stand and tests in situ- and model-based functions to transform these estimates into forest water potential. The retrieval is based on vegetation optical depth data from a tower-based experiment of the SMAPVEX 19–21 campaign for the period from April to October 2019 at Harvard Forest, MA, USA. In addition, comparison and validation with in situ measurements on leaf and xylem water potential as well as on leaf wetness and complex permittivity are foreseen to understand limitations and potentials of the proposed approach. As a first result the radiometer-based water potential estimates of the forest stand are concurrent in time and similar in value with their in situ (xylem) counterparts from single trees in the radiometer footprint.

Members of the Acinetobacter baumannii-calcoaceticus complex are nosocomial pathogens frequently causing multidrug-resistant infections that are increasing at alarming rates. A. baumannii has become the Gram-negative bacterium with the highest rate of multidrug resistance. As such, it is categorized by the World Health Organization as a critical priority for the research and development of new antimicrobial therapies. The zinc-dependent metalloendopeptidase CpaA is a predominant substrate of the type II secretion system (T2SS). CpaA is also a virulence factor of medically relevant Acinetobacter strains that specifically degrade the human glycoprotein coagulation factor XII and not its deglycosylated form, but the mechanism for this specificity is unknown. CpaB is a membrane-anchored T2SS chaperone that interacts with CpaA and is required for its stability and secretion. Here, we report the crystal structure of the CpaAB complex at 2.6-A resolution, revealing four glycan-binding domains in CpaA that were not predicted from its primary sequence and may explain CpaA's glycoprotein-targeting activity. The structure of the complex identified a novel mode for chaperone-protease interactions in which the protease surrounds the chaperone. The CpaAB organization was akin to zymogen inactivation, with CpaB serving as a prodomain that inhibits catalytically active CpaA. CpaB contains a C-terminal tail that appears to block access to the CpaA catalytic site, and functional experiments with truncated variants indicated that this tail is dispensable for CpaA expression and secretion. Our results provide new insight into the mechanism of CpaA secretion and may inform the future development of therapeutic strategies for managing Acinetobacter infections.

Aim This study aims to investigate selective attention in Rett syndrome, a severely disabling neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene. Method The sample included 28 females with Rett syndrome (RTT) and 32 age-matched typically developing controls. We used a classic search task, in conjunction with eye-tracking technology. Each trial included the target and several distractors. The distractors varied in number and differed from targets in either a "single feature" (color or shape), creating a pop-out effect, or in a "conjunction of features" (color and shape), requiring serial search. Children searched for the target in arrays containing five or nine objects; trials ended when the target was fixated (or 4000 ms elapsed). Results Children with Rett syndrome had more difficulty finding the target than typically developing children in both conditions (success rates less than 50% versus 80%) and their success rates were little influenced by display size or age. Even when successful, children with RTT took significantly longer to respond (392 to 574 ms longer), although saccadic latency differences were observed only in the single-feature condition. Both groups showed the expected slowing of saccadic reaction times for larger arrays in the conjunction-feature condition. Search failures in RTT were not related to symptom severity. Conclusions Our findings provide the first evidence that selective attention, the ability to focus on or select a particular element or object in the environment, is compromised by Rett syndrome. They reinforce the notion that gaze-based tasks hold promise for quantifying the cognitive phenotype of RTT.

Nosocomial pathogens of the Acinetobacter calcoaceticus-baumannii (ACB) complex are a cautionary example for the world-wide spread of multi- and pan-drug resistant bacteria. Aiding the urgent demand for novel therapeutic targets, comparative genomics studies between pathogens and their apathogenic relatives shed light on the genetic basis of human-pathogen interaction. Yet, existing studies are limited in taxonomic scope, sensing of the phylogenetic signal, and resolution by largely analyzing genes isolated from their functional contexts. Here, we explored more than 3,000 Acinetobacter genomes in a phylogenomic framework integrating orthology-based phylogenetic profiling and microsynteny conservation analyses. This allowed to delineate gene clusters in the type strain A. baumannii ATCC 19606 whose evolutionary conservation indicates a functional integration of the subsumed genes. These evolutionarily stable gene clusters (ESGCs) reveal metabolic pathways, transcriptional regulators residing next to their targets but also tie together sub-clusters with distinct functions to form higher-order functional modules. We shortlisted 150 ESGCs that either co-emerged with, or are found preferentially in, the pathogenic ACB clade. They unveil, at an unprecedented resolution, the genetic makeup that coincides with the manifestation of the pathogenic phenotype in the last common ancestor of the ACB clade. Key innovations are the remodeling of the regulatory-effector cascade connecting LuxR/LuxI quorum sensing via an intermediate messenger to biofilm formation, the extension of micronutrient scavenging systems, and the increase of metabolic flexibility by exploiting carbon sources that are provided by the human host. Specifically, we could show that only members of the ACB clade use kynurenine as a sole carbon and energy source, a substance produced by humans to fine-tune the antimicrobial innate immune response. In summary, this study provides a rich and unbiased set of novel testable hypotheses on how pathogenic Acinetobacter interact with and ultimately infect their human host. They disclose promising routes for future therapeutic strategies.Author SummaryThe spread of multi- and pan-drug resistant bacterial pathogens is a world-wide threat to human health. Understanding the genetics of host colonization and infection is essential for devising novel ways of treatment. Acinetobacter baumannii, a nosocomial pathogen ranked top by the World Health Organization in the list of bacteria for which novel therapeutic approaches are needed, is a prime example. Here, we have carved out the genetic make-up that distinguishes A. baumannii and its pathogenic next relatives comprising the A. baumannii–calcoaceticus complex from other and mostly apathogenic Acinetobacter species. We found a rich spectrum of pathways and regulatory modules that reveals how the pathogens have modified biofilm formation, iron scavenging, and their carbohydrate metabolism to adapt to their human host. Among these, the capability to metabolize kynurenine is particularly intriguing. Humans produce this substance to contain bacterial invaders and to fine-tune the innate immune response. But A. baumannii and its allies have turned the table. They feed on kynurenine, and thus most likely also dysregulate human immune response. In summary, our study substantially deepens the understanding of how a highly critical pathogen interacts with its host, which substantially eases the identification of novel targets for innovative therapeutic strategies.

Escherichia coli is the leading cause of bloodstream infection (BSI). The incidence of E. coli BSI caused by antibiotic-resistant strains is increasing. We aimed to describe the nationwide incidence and resistance profile of E. coli BSI in Israel and its impact on mortality, to compare E. coli BSI mortality with all-cause mortality, and community-onset with hospital-onset E. coli BSIs.We used mandatory BSI surveillance reports submitted by all Israeli hospitals to the Ministry of Health and the national death registry. All E. coli BSIs from 1 January 2018 to 31 December 31 2019 in patients aged 18 and over were included.A total of 11 113 E. coli BSIs occurred in 10 218 patients; 85% (9012/10 583) were community onset. Median age was 76 (IQR 65-85), and 57% (6304/11 113) of cases occurred in women. The annual incidence was 92.5 per 100 000 population. Antibiotic resistance was frequent and significantly more common in hospital-onset than in community-onset BSI; 65% (1021/1571) vs. 45% (4049/9012) were multidrug-resistant (MDR) (p 0.001). The case fatality rate (CFR) was higher following hospital-onset BSI than community-onset: 23% (276/1214) vs. 12% (926/7620) at 14 days, 31% (378/1214) vs. 16% (1244/7620) at 30 days, and 55% (418/766) vs. 34% (1645/4903) at 1 year (p 0.001 for all comparisons). The 1-year CFR was 47% (1258/2707) for MDR vs. 28% (928/3281) for non-MDR (p 0.001). The annual mortality rate was 31.0 per 100 000 population, comprising 4.2% (31.0/734.8) of all causes of deaths.E. coli BSI carries a high burden, with a large proportion of MDR isolates, which are associated with increased incidence and CFR.

Vegetation cover absorbs and scatters L-band microwave emission measured by SMOS and SMAP satellites. Misrepresentation of this phenomena results in uncertainties when inferring, for instance, surface soil moisture in retrieval algorithms that commonly utilize the tau-omega model which is most applicable for a weakly scattering medium. In this study, we investigate the degree to which multiple-scattering is prevalent over a range of land cover classifications (from lightly vegetated grasslands to dense forests) at the satellite scale by explicitly accounting for multiple-scattering in a first-order radiative transfer model, developed here. Even though the tau-omega model with effective parameters can possibly capture higher-order scattering contributions, deliberately partitioning scattering into different components is required to estimate multiple-scattering properties. Specifically, we aim to determine how one can partition between zeroth and first-order radiative transfer terms within a retrieval algorithm without ancillary information, determine whether this method can detect first-order scattering at the SMAP measurement scale without ancillary information, and quantify the magnitude of detected scattering. A simplified first-order radiative transfer model which characterizes single interactions of microwaves with a scattering medium is developed for implementation within retrieval algorithms. This new emission model is implemented within a recently developed retrieval algorithm, the multi-temporal dual channel algorithm (MT-DCA), which does not require ancillary land use information. Scattering parameters as well as SM and vegetation optical depth (τ) are retrieved simultaneously in Africa and South America using the first year of SMAP brightness temperature measurements on a 36 km grid. Specifically, an introduced time invariant first-order scattering coefficient (ω1) is retrieved representing microwave emission interaction with the canopy. We find that ω1 is typically zero in lightly vegetated biomes and non-zero (~0.06) in 74% of the forest pixels. In forest-dominated pixels, the median first-order emissivity is 0.04, or about 4.3% of a given SMAP radiometer brightness temperature measurement. Additionally, explicitly accounting for first-order scattering terms in the radiative transfer model tends to increase SM and τ retrievals by a median of 0.02 m3/m3 and 0.1, respectively, only in forested regions. This study demonstrates the first attempt to explicitly partition higher-order scattering terms in a retrieval algorithm at a satellite scale and ultimately provides a fundamental understanding and quantification of multiple-scattering from grasslands to forests.

Multidrug-resistantAcinetobacter baumanniiinfections are increasing at alarming rates. Therefore, novel antibiotic-sparing treatments to combat theseA. baumanniiinfections are urgently needed. The development of these interventions would benefit from a better understanding of this bacterium’s pathobiology, which remains poorly understood.A. baumanniiis regarded as an extracellular opportunistic pathogen. However, research onAcinetobacterhas largely focused on common lab strains, such as ATCC 19606, that have been isolated several decades ago. These strains exhibit reduced virulence when compared to recently isolated clinical strains. In this work, we demonstrate that, unlike ATCC 19606, several modernA. baumanniiclinical isolates, including the recent clinical urinary isolate UPAB1, persist and replicate inside macrophages within spacious vacuoles. We show that intracellular replication of UPAB1 is dependent on a functional type I secretion system (T1SS) and pAB5, a large conjugative plasmid that controls the expression of several chromosomally-encoded genes. Finally, we show that UPAB1 escapes from the infected macrophages by a lytic process. To our knowledge, this is the first report of intracellular growth and replication ofA. baumannii. We suggest that intracellular replication within macrophages may contribute to evasion of the immune response, dissemination, and antibiotic tolerance ofA. baumannii.

Multidrug-resistant Acinetobacter baumannii infections are increasing at alarming rates. Therefore, novel antibiotic-sparing treatments to combat these A. baumannii infections are urgently needed. The development of these interventions would benefit from a better understanding of this bacterium’s pathobiology, which remains poorly understood. A. baumannii is regarded as an extracellular opportunistic pathogen. However, research on Acinetobacter has largely focused on common lab strains, such as ATCC 19606, that have been isolated several decades ago. These strains exhibit reduced virulence when compared to recently isolated clinical strains. In this work, we demonstrate that, unlike ATCC 19606, several modern A. baumannii clinical isolates, including the recent clinical urinary isolate UPAB1, persist and replicate inside macrophages within spacious vacuoles. We show that intracellular replication of UPAB1 is dependent on a functional type I secretion system (T1SS) and pAB5, a large conjugative plasmid that controls the expression of several chromosomally-encoded genes. Finally, we show that UPAB1 escapes from the infected macrophages by a lytic process. To our knowledge, this is the first report of intracellular growth and replication of A. baumannii. We suggest that intracellular replication within macrophages may contribute to evasion of the immune response, dissemination, and antibiotic tolerance of A. baumannii., Author summary Acinetobacter baumannii is a nosocomial pathogen that causes multiple types of infection. This bacterium has an alarming predisposition to acquire multi-drug resistance, and infections associated with these strains are linked to greater morbidity and mortality. Therefore, novel antibiotic-sparing treatments to combat these A. baumannii infections are urgently needed. The development of these interventions would benefit from a better understanding of the mechanisms employed by A. baumannii to cause infection. A. baumannii is regarded as an extracellular opportunistic pathogen. However, research on Acinetobacter has largely focused on common lab strains that have been isolated several decades ago. These strains exhibit reduced virulence when compared to recently isolated clinical strains. In this work, we demonstrate that a subset of modern A. baumannii clinical isolates persist and replicate inside macrophages within spacious vacuoles, and identify bacterial factors involved in the process. We propose that replication inside macrophages may contribute to the evasion of the immune response and bacterial dissemination. Antibiotics cannot penetrate the macrophages, and therefore our findings contribute to explain the extremely high tolerance of A. baumannii to antibiotics. Our work opens new avenues for the development of novel therapeutic interventions against this worrisome human pathogen.

The type VI secretion system (T6SS) is a powerful tool deployed by Gram-negative bacteria to antagonize neighboring organisms. Here, we report that Acinetobacter baumannii ATCC 17978 (Ab17978) secretes D-lysine (D-Lys), increasing the extracellular pH and enhancing the peptidoglycanase activity of the T6SS effector Tse4. This synergistic effect of D-Lys on Tse4 activity enables Ab17978 to outcompete Gram-negative bacterial competitors, demonstrating that bacteria can modify their microenvironment to increase their fitness during bacterial warfare. Remarkably, this lethal combination also results in T6SS-mediated killing of Gram-positive bacteria. Further characterization revealed that Tse4 is a bifunctional enzyme consisting of both lytic transglycosylase and endopeptidase activities, thus representing a novel family of modularly organized T6SS PG degrading effectors with an unprecedented impact in antagonistic bacterial interactions.One sentence summaryBy modulating local environmental pH through D-Lys secretion, Acinetobacter baumannii enhances the activity of a bifunctional cell wall-targeting T6SS effector, increasing its killing activity against Gram-negative and -positive competitors.

Nationwide studies on hospital-onset bloodstream infections (HO-BSIs) are scarce. To describe incidence, mortality and antimicrobial resistance (AMR) of HO-BSI caused by eight sentinel bacteria in Israel, we used laboratory-based BSI surveillance data from 1 January 2018 to 31 December 2019. All hospitals reported positive blood cultures growing Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium. We calculated HO-BSI incidence and 14-day, 30-day and 1-year mortality in adults. We performed multivariable logistic regression to identify predictors of 30-day mortality. The study included 6752 HO-BSI events: K. pneumoniae (1659, 22.1%), E. coli (1491, 19.8%), S. aureus (1315, 17.5%), P. aeruginosa (1175, 15.6%), E. faecalis (778, 10.4%), A. baumannii (654, 8.7%), E. faecium (405, 5.4%) and S. pneumoniae (43, 0.6%). Overall incidence was 2.84/1000 admissions (95% CI: 2.77–2.91) and 6.88/10,000 patient-days (95% CI: 6.72–7.05). AMR isolates accounted for 44.2% of events. Fourteen-day, thirty-day and one-year mortality were 30.6% (95% CI: 28.5%–32.8%), 40.2% (95% CI: 38.2%–42.1%) and 66.5% (95% CI: 64.7%–68.3%), respectively. Organisms with highest risk for 30-day mortality (compared with E. coli) were A. baumannii (OR 2.85; 95% CI: 2.3–3.55), E. faecium (OR 2.16; 95% CI: 1.66–2.79) and S. pneumoniae (OR 2.36; 95% CI: 1.21–4.59). Mortality was higher in AMR isolates (OR 1.57; 95% CI: 1.4–1.77). This study highlights the incidence, associated high mortality and important role of antibiotic resistance in HO-BSI.

CpaA is a glycoprotease expressed by members of the Acinetobacter baumannii-calcoaceticus complex, and it is the first bona fide secreted virulence factor identified in these species. Here, we show that CpaA cleaves multiple targets precisely at O-glycosylation sites preceded by a Pro residue. This feature, together with the observation that sialic acid does not impact CpaA activity, makes this enzyme an attractive tool for the analysis of O-linked human protein for biotechnical and diagnostic purposes. Previous work identified proteins involved in blood coagulation as targets of CpaA. Our work broadens the set of targets of CpaA, pointing toward additional roles in bacterium-host interactions. We propose that CpaA belongs to an expanding class of functionally defined glycoproteases that targets multiple O-linked host glycoproteins., Glycans decorate proteins and affect their biological function, including protection against proteolytic degradation. However, pathogenic, and commensal bacteria have evolved specific glycoproteases that overcome the steric impediment posed by carbohydrates, cleaving glycoproteins precisely at their glycosylation site(s). Medically relevant Acinetobacter strains employ their type II secretion system (T2SS) to secrete the glycoprotease CpaA, which contributes to virulence. Previously, CpaA was shown to cleave two O-linked glycoproteins, factors V and XII, leading to reduced blood coagulation. In this work, we show that CpaA cleaves a broader range of O-linked human glycoproteins, including several glycoproteins involved in complement activation, such as CD55 and CD46. However, only CD55 was removed from the cell surface, while CD46 remained unaltered during the Acinetobacter nosocomialis infection assay. We show that CpaA has a unique consensus target sequence that consists of a glycosylated serine or threonine residue after a proline residue (P-S/T), and its activity is not affected by sialic acids. Molecular modeling and mutagenesis analysis of CpaA suggest that the indole ring of Trp493 and the ring of the Pro residue in the substrate form a key interaction that contributes to CpaA sequence selectivity. Similar bacterial glycoproteases have recently gained attention as tools for proteomic analysis of human glycoproteins, and CpaA appears to be a robust and attractive new component of the glycoproteomics toolbox. Combined, our work provides insight into the function and possible application of CpaA, a member of a widespread class of broad-spectrum bacterial glycoproteases involved in host-pathogen interactions.