Genome sequences of 12 bacterial isolates obtained from the urine of pregnant women

The presence of bacteria in urine can pose significant risks during pregnancy. However, there are few reference genome strains for many common urinary bacteria. We isolated 12 urinary strains of Streptococcus, Staphylococcus, Citrobacter, Gardnerella, and Lactobacillus. These strains and their genomes are now available to the research community

Discovery and characterization of a new class of O-linking oligosaccharyltransferases from the Moraxellaceae family

Bacterial protein glycosylation is commonly mediated by oligosaccharyltransferases (OTases) that transfer oligosaccharides en bloc from preassembled lipid-linked precursors to acceptor proteins. Natively, O-linking OTases usually transfer a single repeat unit of the O-antigen or capsular polysaccharide to the side chains of serine or threonine on acceptor proteins. Three major families of bacterial O-linking OTases have been described: PglL, PglS, and TfpO. TfpO is limited to transferring short oligosaccharides both in its native context and when heterologously expressed in glycoengineered Escherichia coli. On the other hand, PglL and PglS can transfer long-chain polysaccharides when expressed in glycoengineered E. coli. Herein, we describe the discovery and functional characterization of a novel family of bacterial O-linking OTases termed TfpM from Moraxellaceae bacteria. TfpM proteins are similar in size and sequence to TfpO enzymes but can transfer long-chain polysaccharides to acceptor proteins. Phylogenetic analyses demonstrate that TfpM proteins cluster in distinct clades from known bacterial OTases. Using a representative TfpM enzyme from Moraxella osloensis, we determined that TfpM glycosylates a C-terminal threonine of its cognate pilin-like protein and identified the minimal sequon required for glycosylation. We further demonstrated that TfpM has broad substrate tolerance and can transfer diverse glycans including those with glucose, galactose, or 2-N-acetyl sugars at the reducing end. Last, we find that a TfpM-derived bioconjugate is immunogenic and elicits serotype-specific polysaccharide IgG responses in mice. The glycan substrate promiscuity of TfpM and identification of the minimal TfpM sequon renders this enzyme a valuable additional tool for expanding the glycoengineering toolbox

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

Development and immunogenicity of a prototype multivalent Group B Streptococcus bioconjugate vaccine

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Foraging Behavior and Success of a Mesopelagic Predator in the Northeast Pacific Ocean: Insights from a Data-Rich Species, the Northern Elephant Seal

The mesopelagic zone of the northeast Pacific Ocean is an important foraging habitat for many predators, yet few studies have addressed the factors driving basin-scale predator distributions or inter-annual variability in foraging and breeding success. Understanding these processes is critical to reveal how conditions at sea cascade to population-level effects. To begin addressing these challenging questions, we collected diving, tracking, foraging success, and natality data for 297 adult female northern elephant seal migrations from 2004 to 2010. During the longer post-molting migration, individual energy gain rates were significant predictors of pregnancy. At sea, seals focused their foraging effort along a narrow band corresponding to the boundary between the sub-arctic and sub-tropical gyres. In contrast to shallow-diving predators, elephant seals target the gyre-gyre boundary throughout the year rather than follow the southward winter migration of surface features, such as the Transition Zone Chlorophyll Front. We also assessed the impact of added transit costs by studying seals at a colony near the southern extent of the species’ range, 1,150 km to the south. A much larger proportion of seals foraged locally, implying plasticity in foraging strategies and possibly prey type. While these findings are derived from a single species, the results may provide insight to the foraging patterns of many other meso-pelagic predators in the northeast Pacific Ocean

CXCR2 Signaling Protects Oligodendrocytes and Restricts Demyelination in a Mouse Model of Viral-Induced Demyelination

BACKGROUND: The functional role of ELR-positive CXC chemokines during viral-induced demyelination was assessed. Inoculation of the neuroattenuated JHM strain of mouse hepatitis virus (JHMV) into the CNS of susceptible mice results in an acute encephalomyelitis that evolves into a chronic demyelinating disease, modeling white matter pathology observed in the human demyelinating disease Multiple Sclerosis. METHODOLOGY/PRINCIPAL FINDINGS: JHMV infection induced the rapid and sustained expression of transcripts specific for the ELR+ chemokine ligands CXCL1 and CXCL2, as well as their binding receptor CXCR2, which was enriched within the spinal cord during chronic infection. Inhibiting CXCR2 signaling with neutralizing antiserum significantly (p<0.03) delayed clinical recovery. Moreover, CXCR2 neutralization was associated with an increase in the severity of demyelination that was independent of viral recrudescence or modulation of neuroinflammation. Rather, blocking CXCR2 was associated with increased numbers of apoptotic cells primarily within white matter tracts, suggesting that oligodendrocytes were affected. JHMV infection of enriched oligodendrocyte progenitor cell (OPC) cultures revealed that apoptosis was associated with elevated expression of cleaved caspase 3 and muted Bcl-2 expression. Inclusion of CXCL1 within JHMV infected cultures restricted caspase 3 cleavage and increased Bcl-2 expression that was associated with a significant (p<0.001) decrease in apoptosis. CXCR2 deficient oligodendrocytes were refractory to CXCL1 mediated protection from JHMV-induced apoptosis, readily activating caspase 3 and down regulating Bcl-2. CONCLUSION/SIGNIFICANCE: These findings highlight a previously unappreciated role for CXCR2 signaling in protecting oligodendrocyte lineage cells from apoptosis during inflammatory demyelination initiated by viral infection of the CNS

Ozone depletion, ultraviolet radiation, climate change and prospects for a sustainable future

Changes in stratospheric ozone and climate over the past 40-plus years have altered the solar ultraviolet (UV) radiation conditions at the Earth's surface. Ozone depletion has also contributed to climate change across the Southern Hemisphere. These changes are interacting in complex ways to affect human health, food and water security, and ecosystem services. Many adverse effects of high UV exposure have been avoided thanks to the Montreal Protocol with its Amendments and Adjustments, which have effectively controlled the production and use of ozone-depleting substances. This international treaty has also played an important role in mitigating climate change. Climate change is modifying UV exposure and affecting how people and ecosystems respond to UV; these effects will become more pronounced in the future. The interactions between stratospheric ozone, climate and UV radiation will therefore shift over time; however, the Montreal Protocol will continue to have far-reaching benefits for human well-being and environmental sustainability.Peer reviewe

Solar ultraviolet radiation and ozone depletion-driven climate change: Effects on terrestrial ecosystems

In this assessment we summarise advances in our knowledge of how UV-B radiation (280-315 nm), together with other climate change factors, influence terrestrial organisms and ecosystems. We identify key uncertainties and knowledge gaps that limit our ability to fully evaluate the interactive effects of ozone depletion and climate change on these systems. We also evaluate the biological consequences of the way in which stratospheric ozone depletion has contributed to climate change in the Southern Hemisphere. Since the last assessment, several new findings or insights have emerged or been strengthened. These include: (1) the increasing recognition that UV-B radiation has specific regulatory roles in plant growth and development that in turn can have beneficial consequences for plant productivity via effects on plant hardiness, enhanced plant resistance to herbivores and pathogens, and improved quality of agricultural products with subsequent implications for food security; (2) UV-B radiation together with UV-A (315-400 nm) and visible (400-700 nm) radiation are significant drivers of decomposition of plant litter in globally important arid and semi-arid ecosystems, such as grasslands and deserts. This occurs through the process of photodegradation, which has implications for nutrient cycling and carbon storage, although considerable uncertainty exists in quantifying its regional and global biogeochemical significance; (3) UV radiation can contribute to climate change via its stimulation of volatile organic compounds from plants, plant litter and soils, although the magnitude, rates and spatial patterns of these emissions remain highly uncertain at present. UV-induced release of carbon from plant litter and soils may also contribute to global warming; and (4) depletion of ozone in the Southern Hemisphere modifies climate directly via effects on seasonal weather patterns (precipitation and wind) and these in turn have been linked to changes in the growth of plants across the Southern Hemisphere. Such research has broadened our understanding of the linkages that exist between the effects of ozone depletion, UV-B radiation and climate change on terrestrial ecosystems