Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis.

Streptococcus pneumoniaebacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement.

Capsule gene regulation in Bacillus anthracis and implications for virulence

The poly-D-glutamic acid capsule of Bacillus anthracis is considered essential for lethal anthrax disease. Yet investigations of capsule function have been limited primarily to attenuated B. anthracis strains lacking certain genetic elements. In work presented in this thesis, I constructed and characterized a genetically complete (pXO1 + pXO2+) B. anthracis strain (UT500) and isogenic mutants deleted for two previously identified capsule gene regulators, atxA and acpA, and a newly-identified regulator, acpB. Results of transcriptional analysis and microscopy revealed that atxA controls expression of the first gene of the capsule biosynthesis operon, capB, via positive transcriptional regulation of acpA and acpB. acpA and acpB appear to be partial functional homologs. Deletion of either gene alone has little effect on capsule synthesis. However, a mutant deleted for both acpA and acpB is noncapsulated. Thus, in contrast to previously published models, my results suggest that atxA is the master regulator of cap gene expression in a genetically complete strain. A detailed transcriptional analysis of capB and the regulatory genes was performed to establish the effects of the regulators and CO2/bicarbonate on specific mRNAs of target genes. CO2/bicarbonate is a well-established signal for B. anthracis capsule synthesis in culture. Taqman RT-PCR results indicated that growth in the presence of elevated CO2 greatly increased expression of acpA, acpB and capB but not atxA. 5′ end mapping of capB and acpA revealed atxA-regulated and atxA-independent transcriptional start sites for both genes. All atxA-regulated start sites were also CO2-regulated. A single atxA-independent start site was identified 5 ′ of acpB. However, RT-PCR analysis indicated that capD and acpB are co-transcribed. Thus, it is likely that atxA-mediated control of acpB expression occurs via transcriptional activation of the atxA-regulated start sites of capB. Finally, I examined the contribution of the B. anthracis capsule to virulence. The virulence of the parent strain, mutants deleted for the capsule biosynthesis genes ( capBCAD), and mutants missing the capsule regulator genes was compared using a mouse model for inhalation anthrax. The data indicate that in this model, capsule is essential for virulence. Mice survived infection with the noncapsulated capBCAD and acpA acpB mutants. These mutants initiated germination in the lung, but did not disseminate to the spleen. The acpA mutant had an LD50 value similar to the parent strain and was able to disseminate and cause lethal infection. Unexpectedly, the acpB mutant had a higher LD 50 and a reduced ability to disseminate. During in vitro culture, the acpB single mutant produces capsule and toxin similar to the parent strain. It is likely that acpB regulates the expression of downstream genes that contribute to the virulence of B. anthracis. ^

Empowering Teachers as Leaders: A Hard Sell

Despite emphasis on preparing teachers as leaders, teacher educators realize that the transition of classroom practitioners into school leaders is fraught with many obstacles. This session addresses some of these obstacles, describes strategies and opportunities that we have used in our graduate master’s degree programs for teachers that support professionals as they make this change. The session will present evidence on the results of our efforts in terms of teachers’ performances within their programs and in the field after they graduate.

Johannes Daniel Hard, Hüftbild

Signatur des Originals: S 36/G03135

Why the Village is so Hard to Find: Challenging Ourselves, Transforming Our Helping Systems

Keynote address presented by Roger Friedman, PhD, LCSW at the Family Preservation Institute Annual Conference, San Antonio, Texas, September 9, 2004. Looking at Language and Concepts Looking closely at certain language that we use helps us understand how we think about our work and our world—and ultimately, it helps us understand ourselves better. The term "village " as used in the title of the paper and in many of our professional conversations is worthy of such an inquiry

Succession of benthic hard-bottom communities in the shallow sublitoral of Comau Fjord, Chile

Succession was already studied over decades. The present thesis investigated the succession on hard substrate at two different study sites within the fjord Comau, Chile. Nine plates were installed at both sites (mouth of fjord and inner fjord) and photographed over three years. Additionally the natural community was recorded and a ground truthing was carried out to verify the analyzed species. Respectively at both sites over 50 different species were identified. Abundance data decreased with only one exception continuously, whereas the percentage cover increased. But the communities on the recruitment plates do still not reach the community structure of the natural environment. The present data showed that the hard-bottom succession in the fjord Comau is best described by the TOLERANCE MODEL (Connell & Slatyer, 1977). An important species of the natural community is the stony coral Desmophyllum dianthus, which normally (outside the fjord) grows beneath 1000 m water depth. The results of this work indicate that the mature community is not reached after 36 months.