Community-acquired pneumonia related to intracellular pathogens

Community-acquired pneumonia (CAP) is associated with high rates of morbidity and mortality worldwide; the annual incidence of CAP among adults in Europe has ranged from 1.5 to 1.7 per 1000 population. Intracellular bacteria are common causes of CAP. However, there is considerable variation in the reported incidence between countries and change over time. The intracellular pathogens that are well established as causes of pneumonia are Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Chlamydophila psittaci, and Coxiella burnetii. Since it is known that antibiotic treatment for severe CAP is empiric and includes coverage of typical and atypical pathogens, microbiological diagnosis bears an important relationship to prognosis of pneumonia. Factors such as adequacy of initial antibiotic or early de-escalation of therapy are important variables associated with outcomes, especially in severe cases. Intracellular pathogens sometimes appear to cause more severe disease with respiratory failure and multisystem dysfunction associated with fatal outcomes. The clinical relevance of intracellular pathogens in severe CAP has not been specifically investigated. We review the prevalence, general characteristics, and outcomes of severe CAP cases caused by intracellular pathogens

Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes

Shiga-toxigenic Escherichia coli (STEC) use subtilase cytotoxin (SubAB) to interfere with adaptive immunity. Its inhibition of immunoglobulin secretion is both rapid and profound. SubAB favors cleavage of the newly synthesized immunoglobulin heavy chain–binding protein (BiP) to yield a C-terminal fragment that contains BiP’s substrate-binding domain. In the absence of its regulatory nucleotide-binding domain, the SubAB-cleaved C-terminal BiP fragment remains tightly bound to newly synthesized immunoglobulin light chains, resulting in retention of light chains in the endoplasmic reticulum (ER). Immunoglobulins are thus detained in the ER, making impossible the secretion of antibodies by SubAB-treated B cells. The inhibitory effect of SubAB is highly specific for antibody secretion, because other secretory proteins such as IL-6 are released normally from SubAB-treated B cells. Although SubAB also causes BiP cleavage in HepG2 hepatoma cells, (glyco)protein secretion continues unabated in SubAB-exposed HepG2 cells. This specific block in antibody secretion is a novel means of immune evasion for STEC. The differential cleavage of newly synthesized versus "aged" BiP by SubAB in the ER provides insight into the architecture of the ER compartments involved.National Institutes of Health (U.S.)Cancer Research Institute (New York, N.Y.

Dissociation from BiP and Retrotranslocation of Unassembled Immunoglobulin Light Chains Are Tightly Coupled to Proteasome Activity

Unassembled immunoglobulin light chains expressed by the mouse plasmacytoma cell line NS1 (κ(NS1)) are degraded in vivo with a half-life of 50–60 min in a way that closely resembles endoplasmic reticulum (ER)-associated degradation (Knittler et al., 1995). Here we show that the peptide aldehydes MG132 and PS1 and the specific proteasome inhibitor lactacystin effectively increased the half-life of κ(NS1), arguing for a proteasome-mediated degradation pathway. Subcellular fractionation and protease protection assays have indicated an ER localization of κ(NS1) upon proteasome inhibition. This was independently confirmed by the analysis of the folding state of κ(NS1) and size fractionation experiments showing that the immunoglobulin light chain remained bound to the ER chaperone BiP when the activity of the proteasome was blocked. Moreover, kinetic studies performed in lactacystin-treated cells revealed a time-dependent increase in the physical stability of the BiP–κ(NS1) complex, suggesting that additional proteins are present in the older complex. Together, our data support a model for ER-associated degradation in which both the release of a soluble nonglycosylated protein from BiP and its retrotranslocation out of the ER are tightly coupled with proteasome activity

Veränderungen in der sozialen und ethnischen Zusammensetzung der Schülerschaft aus demografischer Perspektive

In diesem Beitrag wird untersucht, welche Veränderungen in der ethnischen und sozialen Zusammensetzung der Bevölkerung im Schul- und Vorschulalter festzustellen sind und welche Konsequenzen sich hieraus für die Bildungsbeteiligung und damit für die Entwicklung des Bildungsstands in der Bevölkerung ergeben könnten. Auf Basis der Mikrozensuserhebung 2008 können hinsichtlich der Herkunftsregion der Eltern mehrere Migrantengruppen identifiziert werden, in denen die Kinder trotz des niedrigen Bildungstands der Eltern und vergleichsweise geringer sozioökonomischer Ressourcen in der Familie größere Chancen auf einen Bildungsaufstieg haben als Kinder aus Familien ohne Migrationshintergrund. In bildungsfernen Familien ohne Migrationshintergrund finden sich hingegen eine geringere Tendenz zu aufstiegsorientierten Bildungsentscheidungen und eine stärkere Bindung des Bildungsverhaltens an die ökonomische und soziale Lebenslage. Die Analysen liefern Hinweise darauf, dass der bildungsbezogene Hintergrund und die sozioökonomischen Ressourcen in den Familien insgesamt bedeutender sind für die Entwicklung des Bildungsniveaus in der Bevölkerung als Merkmale der Zuwanderung und der ethnischen Herkunft. (DIPF/Orig.)In this paper, we examine current changes in the ethnic and social composition of the preschool and school aged population as well as the consequences these changes may have for educational participation and thus for overall educational attainment in the near future. Based on the micro-census 2008 survey, we identify groups of migrants by region of parents\u27 origin where children - despite low levels of parents\u27 education and comparatively few socioeconomic resources - have greater chances of upward educational mobility than non-migrant children. By contrast, children from less educated, nonmigrant families show a much lower tendency to be upwardly mobile, and educational choices are more closely tied to the economic and social background. Thus, our analysis provides evidence that educational background and socio-economic resources in the students\u27 families are of greater importance for the overall development of educational attainment in Germany than characteristics of migration and ethnicity. (DIPF/Orig.

Multilocus Sequence Typing (MLST) of Chlamydiales

Developed two decades ago as a molecular method to provide definite characterization of a bacterial isolate, Multilocus Sequence Typing (MLST) is today globally adopted as a universal fine-detailed molecular typing tool and has been applied to numerous pathogenic and nonpathogenic bacterial as well eukaryotic organisms. MLST utilizes DNA sequence of several conserved housekeeping (HK) genes which are assigned an allelic number, which then collectively constitute an allelic profile or sequence type (ST), a “molecular barcode” of the interrogated bacterial strain or a eukaryotic organism. Here, we describe the principles and molecular approaches for generating MLST data for an analysis of a bacteria in the order Chlamydiales, using a Chlamydia pecorum-specific MLST scheme as an example

Avian Chlamydiosis

Recent findings in research on avian chlamydiosis include an increase in the reported prevalence of Chlamydia (C.) psittaci in poultry flocks, detailed descriptions of molecular processes governing the course of infection in vivo, as well as the discovery of new chlamydial species. Here we review the major advances of the last 6 years. In particular, we suggest that the observed re-emergence of C. psittaci infections in domestic poultry are due to a reduction in the use of antibiotics and better diagnostic assays. Cellular and animal models have significantly contributed to improving our understanding of the pathogenesis, including the events leading to systemic disease. The elucidation of host-pathogen interactions revealed the efficiency of C. psittaci in proliferating and disseminating despite the action of pro-inflammatory mediators and other factors during host immune response. Finally, the recent introduction of C. avium and C. gallinacea sheds new light on the epidemiology and aetiopathology of avian chlamydiosis