Gardnerella vaginalis promotes group B Streptococcus vaginal colonization, enabling ascending uteroplacental infection in pregnant mice

BACKGROUND: Group B Streptococcus is a common vaginal bacterium and the leading cause of invasive fetoplacental infections. Group B Streptococcus in the vagina can invade through the cervix to cause ascending uteroplacental infections or can be transmitted to the neonate during vaginal delivery. Some studies have found that women with a dysbiotic polymicrobial or Lactobacillus-depleted vaginal microbiota are more likely to harbor group B Streptococcus. Gardnerella vaginalis is often the most abundant bacteria in the vaginas of women with dysbiosis, while being detected at lower levels in most other women, and has been linked with several adverse pregnancy outcomes. Mouse models of group B Streptococcus and Gardnerella vaginalis colonization have been reported but, to the best of our knowledge, the two have not been studied together. The overarching idea driving this study is that certain members of the dysbiotic vaginal microbiota, such as Gardnerella vaginalis, may directly contribute to the increased rate of group B Streptococcus vaginal colonization observed in women with vaginal dysbiosis. OBJECTIVE: We used a mouse model to test the hypothesis that vaginal exposure to Gardnerella vaginalis may facilitate colonization and/or invasive infection of the upper reproductive tract by group B Streptococcus during pregnancy. STUDY DESIGN: Timed-pregnant mice were generated using an allogeneic mating strategy with BALB/c males and C57Bl/6 females. Dams were vaginally inoculated at gestational day 14 with group B Streptococcus alone (using a 10-fold lower dose than previously reported models) or coinoculated with group B Streptococcus and Gardnerella vaginalis. Bacterial titers were enumerated in vaginal, uterine horn, and placental tissues at gestational day 17. The presence (Fisher exact tests) and levels (Mann-Whitney U tests) of bacterial titers were compared between mono- and coinoculated dams in each compartment. Relative risks were calculated for outcomes that occurred in both groups. Tissue samples were also examined for evidence of pathophysiology. RESULTS: Inoculation of pregnant mice with 10 CONCLUSION: These data suggest that Gardnerella vaginalis vaginal exposure can promote group B Streptococcus vaginal colonization, resulting in a greater likelihood of invasive perinatal group B Streptococcus infections. These findings suggest that future clinical studies should examine whether the presence of Gardnerella vaginalis is a risk factor for group B Streptococcus vaginal colonization in women. Because Gardnerella vaginalis can also be present in women without bacterial vaginosis, these findings may be relevant both inside and outside of the context of vaginal dysbiosis

The identification of Staphylococcus aureus factors required for pathogenicity and growth in human blood

Staphylococcus aureus is a human commensal but also has devastating potential as an opportunist pathogen. S. aureus bacteraemia is often associated with an adverse outcome. To identify potential targets for novel control approaches we have identified S. aureus components that are required for growth on human blood. An ordered transposon mutant library was screened, identifying 9 genes involved specifically in haemolysis or growth on human blood agar compared to the parental strain. Three genes (purA, purB and pabA) were subsequently found to be required for pathogenesis in the zebrafish embryo infection model. The pabA growth defect was specific to the red blood cell component of human blood, showing no growth difference compared to the parental strain on human serum, human plasma, sheep or horse blood. PabA is required in the tetrahydrofolate (THF) biosynthesis pathway. The pabA growth defect was found to be due to a combination of loss of THF-dependent dTMP production by the enzyme ThyA and an increased demand for pyrimidines in human blood. Our work highlights pabA and the pyrimidine salvage pathway as potential targets for novel therapeutics and suggests a previously undefined role for a human blood factor in the activity of sulphonamide antibiotics

Correlation of Group C Meningococcal Conjugate Vaccine Response with B- and T-Lymphocyte Activity

Despite the success of conjugate vaccination against meningococcal group C (MenC) disease, post-vaccination, some individuals still exhibit rapid waning of initially protective bactericidal antibody levels. The mechanism of this relative loss of humoral protection remains undetermined. In this report we have investigated the relationship between T- and B-cell activation and co-stimulation and the loss of protective antibody titers. We have found that healthy volunteers who lose protective MenC antibody levels one year after receipt of glycoconjugate vaccine exhibit no detectable cellular defect in polyclonal B- or T-cell activation, proliferation or the B-memory pool. This suggests that the processes underlying the more rapid loss of antibody levels are independent of defects in either initial T- or B-cell activation

Associations between the vaginal microbiome and Candida colonization in women of reproductive age

Background The composition of bacteria within the vaginal microbiome has garnered a lot of recent attention and has been associated with reproductive health and disease. Despite the common occurrence of yeast (primarily Candida) within the vaginal microbiome, there is still an incomplete picture of relationships between yeast and bacteria (especially lactobacilli), as well as how such associations are governed. Such relationships could be important to a more holistic understanding of the vaginal microbiome and its connection to reproductive health. Objective To perform molecular characterization of clinical specimens to define associations between vaginal bacteria (especially Lactobacillus species) and Candida colonization. In vitro studies were conducted to test the two most common dominant Lactobacillus species (Lactobacillus crispatus and Lactobacillus iners) in their ability to inhibit Candida growth and to examine the basis for such inhibition. Study Design A nested cross-sectional study of reproductive age women from the Contraceptive CHOICE Project was conducted. Vaginal swabs from 299 women were selected to balance race and BV status, resulting in similar representation of black and white women in each of the three Nugent score categories [normal (0-3), intermediate (4-6), and bacterial vaginosis (7-10)]. Sequencing of the 16S ribosomal gene (V4 region) was used to determine the dominant Lactobacillus species present (primarily L. iners and L. crispatus), defined as >50% of the community. Subjects without dominance by a single Lactobacillus species were classified as Diverse. A Candida-specific qPCR targeting the internally transcribed spacer 1 (ITS1) was validated using vaginal samples collected from a second cohort of women and used to assess Candida colonization. 255 nonpregnant women with sufficient bacterial biomass for analysis were included in the final analysis. Generalized linear models were employed to evaluate associations between Lactobacillus dominance, sociodemographic and risk characteristics and vaginal Candida colonization. In separate in vitro studies, the potential of cell-free supernatants from L. crispatus and L. iners cultures to inhibit Candida growth was evaluated. Results Forty-two women (16%) were vaginally colonized with Candida. Microbiomes characterized as Diverse (38%), L. iners-dominant (39%), and L. crispatus-dominant (20%) were the most common. The microbiome, race and Candida colonization co-varied with a higher prevalence of Candida among black women and L. iners-dominant communities compared to white women and L. crispatus-dominant communities. L. iners-dominant communities were more likely to harbor Candida than L. crispatus-dominant communities (OR = 2.85, 95% CI: 1.03 to 7.21; Fisher’s Exact, p = 0.048). In vitro, L. crispatus produced greater concentrations of lactic acid and exhibited significantly more pH-dependent growth inhibition of C. albicans, suggesting a potential mechanism for the clinical observations. Conclusion In nonpregnant women, L. iners-dominant communities were significantly more likely to harbor Candida than L. crispatus-dominant communities, suggesting that Lactobacillus species have different relationships with Candida. In vitro experiments indicate that L. crispatus may impede Candida colonization more effectively than L. iners through a greater production of lactic acid

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Meeting the cultural and service needs of Arabic international students by using QFD

Quality has become an important factor in global competition for many reasons. Intensive global competition and the demand for better quality by customers has led organizations to realize the benefits of providing quality products and services in order to successfully compete and survive. Higher education institutions are one example of these organisations. Higher education institutions work in an intensive competitive environment worldwide driven by increasing demands for learning by local and international students. As a result, the managers of these sectors have realized that improving the quality of services is important for achieving customer satisfaction which can help survival in an internationally competitive market. To do this, it is necessary for organizations to know their customers and identify their requirements. To this end, many higher education institutions have adopted principles of total quality management (TQM) to improve their education quality which leads to better performance through involvement of every department to achieve excellence in business. This chapter considers the importance of measuring quality in order to assist universities to proactively manage the design and improvement of the social and academic experiences of postgraduate international students, and plan management decision-making processes to deliver high-quality services in a globalized business of provision of higher education. Higher education institutions must operate effectively and efficiently and be able to deliver quality programs, by seeking to better understand the needs of their customers to be competitive in this market space

Garotas de loja, história social e teoria social [Shop Girls, Social History and Social Theory]

Shop workers, most of them women, have made up a significant proportion of Britain’s labour force since the 1850s but we still know relatively little about their history. This article argues that there has been a systematic neglect of one of the largest sectors of female employment by historians and investigates why this might be. It suggests that this neglect is connected to framings of work that have overlooked the service sector as a whole as well as to a continuing unease with the consumer society’s transformation of social life. One element of that transformation was the rise of new forms of aesthetic, emotional and sexualised labour. Certain kinds of ‘shop girls’ embodied these in spectacular fashion. As a result, they became enduring icons of mass consumption, simultaneously dismissed as passive cultural dupes or punished as powerful agents of cultural destruction. This article interweaves the social history of everyday shop workers with shifting representations of the ‘shop girl’, from Victorian music hall parodies, through modernist social theory, to the bizarre bombing of the Biba boutique in London by the Angry Brigade on May Day 1971. It concludes that progressive historians have much to gain by reclaiming these workers and the service economy that they helped create

Staphylococcus aureus Induces Eosinophil Cell Death Mediated by α-hemolysin

Staphylococcus aureus, a major human pathogen, exacerbates allergic disorders, including atopic dermatitis, nasal polyps and asthma, which are characterized by tissue eosinophilia. Eosinophils, via their destructive granule contents, can cause significant tissue damage, resulting in inflammation and further recruitment of inflammatory cells. We hypothesised that the relationship between S. aureus and eosinophils may contribute to disease pathology. We found that supernatants from S. aureus (SH1000 strain) cultures cause rapid and profound eosinophil necrosis, resulting in dramatic cell loss within 2 hours. This is in marked contrast to neutrophil granulocytes where no significant cell death was observed (at equivalent dilutions). Supernatants prepared from a strain deficient in the accessory gene regulator (agr) that produces reduced levels of many important virulence factors, including the abundantly produced α-hemolysin (Hla), failed to induce eosinophil death. The role of Hla in mediating eosinophil death was investigated using both an Hla deficient SH1000-modified strain, which did not induce eosinophil death, and purified Hla, which induced concentration-dependent eosinophil death via both apoptosis and necrosis. We conclude that S. aureus Hla induces aberrant eosinophil cell death in vitro and that this may increase tissue injury in allergic disease

An Insect Herbivore Microbiome with High Plant Biomass-Degrading Capacity

Herbivores can gain indirect access to recalcitrant carbon present in plant cell walls through symbiotic associations with lignocellulolytic microbes. A paradigmatic example is the leaf-cutter ant (Tribe: Attini), which uses fresh leaves to cultivate a fungus for food in specialized gardens. Using a combination of sugar composition analyses, metagenomics, and whole-genome sequencing, we reveal that the fungus garden microbiome of leaf-cutter ants is composed of a diverse community of bacteria with high plant biomass-degrading capacity. Comparison of this microbiome's predicted carbohydrate-degrading enzyme profile with other metagenomes shows closest similarity to the bovine rumen, indicating evolutionary convergence of plant biomass degrading potential between two important herbivorous animals. Genomic and physiological characterization of two dominant bacteria in the fungus garden microbiome provides evidence of their capacity to degrade cellulose. Given the recent interest in cellulosic biofuels, understanding how large-scale and rapid plant biomass degradation occurs in a highly evolved insect herbivore is of particular relevance for bioenergy