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Background: Folate plays an essential role in the prevention of neural tube defects, yet little is known about the folate status of women of reproductive age or to what degree the general population is aware of the importance of folate in early-life development. We aimed to determine folate status in women of reproductive age and pregnant women in Switzerland, and to assess folate awareness in the Swiss population., Methods: In a convenience sample of 171 women of reproductive age and 177 pregnant women throughout Switzerland, we measured red blood cell (RBC) folate concentration. In a second convenience sample ( n = 784, men and women) we assessed folate knowledge with an online survey., Results: RBC folate concentration (median interquartile range) was 442 (366, 564) nmol/L in women of reproductive age and 873 (677, 1177) nmol/L in pregnant women. Folate deficiency (RBC folate <340 nmol/L) was found in 19.9% of women of reproductive age and 2.8% of pregnant women, while 91.8% of women of reproductive age and 52.0% of pregnant women showed folate concentrations indicating an elevated risk of neural tube defects (RBC folate <906 nmol/L). The online survey showed that a high proportion (≥88%) of participants were aware of folate's role in neural tube defect (NTD) prevention and fetal development, yet knowledge about dietary sources and national recommendations of folate supplementation when planning pregnancy were limited., Conclusion: The high prevalence of folate inadequacy in Swiss women suggests an elevated risk of neural tube defects and calls for urgent measures to increase folate intakes.

The water-borne bacterium Legionella pneumophila replicates in environmental protozoa and upon inhalation destroys alveolar macrophages, thus causing a potentially fatal pneumonia termed 'Legionnaires' disease'. L. pneumophila employs the Legionella quorum sensing (Lqs) system to control its life cycle, pathogen-host cell interactions, motility and natural competence. Signaling through the Lqs system occurs through the α-hydroxyketone compound Legionella autoinducer-1 (LAI-1) and converges on the prototypic response regulator LqsR, which dimerizes upon phosphorylation of the conserved aspartate, D 108 . In this study, we determine the high-resolution structure of monomeric LqsR. The structure reveals a receiver domain adopting a canonical (βα) 5 fold, which is connected through an additional sixth helix and an extended α5-helix to a novel output domain. The two domains delineate a mainly positively charged groove, and the output domain adopts a five-stranded antiparallel β-sheet fold similar to nucleotide-binding proteins. Structure-based mutagenesis identified amino acids critical for LqsR phosphorylation and dimerization. Upon phosphorylation, the LqsR D172A and LqsR D302N/E303Q mutant proteins dimerized even more readily than wild-type LqsR, and no evidence for semi-phosphorylated heterodimers was obtained. Taken together, the high-resolution structure of LqsR reveals functionally relevant amino acid residues implicated in signal transduction of the prototypic response regulator., (© 2020 John Wiley & Sons Ltd.)

Retrograde trafficking from the endosomal system through the Golgi apparatus back to the endoplasmic reticulum is an essential pathway in eukaryotic cells, serving to maintain organelle identity and to recycle empty cargo receptors delivered by the secretory pathway. Intracellular replication of several bacterial pathogens, including Legionella pneumophila , is restricted by the retrograde trafficking pathway. L. pneumophila employs the Icm/Dot type IV secretion system (T4SS) to form the replication-permissive Legionella -containing vacuole (LCV), which is decorated with multiple components of the retrograde trafficking machinery as well as retrograde cargo receptors. The L. pneumophila effector protein RidL is secreted by the T4SS and interferes with retrograde trafficking. Here, we review recent evidence that the LCV interacts with the retrograde trafficking pathway, discuss the possible sites of action and function of RidL in the retrograde route, and put forth the hypothesis that the LCV is an acceptor compartment of retrograde transport vesicles.

Legionella pneumophila can cause Legionnaires' disease and replicates intracellularly in a distinct Legionella-containing vacuole (LCV). LCV formation is a complex process that involves a plethora of type IV-secreted effector proteins. The effector RidL binds the Vps29 retromer subunit, blocks retrograde vesicle trafficking, and promotes intracellular bacterial replication. Here, we reveal that the 29-kDa N-terminal domain of RidL (RidL 2-281 ) adopts a "foot-like" fold comprising a protruding β-hairpin at its "heel". The deletion of the β-hairpin, the exchange to Glu of Ile 170 in the β-hairpin, or Leu 152 in Vps29 abolishes the interaction in eukaryotic cells and in vitro. RidL 2-281 or RidL displace the Rab7 GTPase-activating protein (GAP) TBC1D5 from the retromer and LCVs, respectively, and TBC1D5 promotes the intracellular growth of L. pneumophila. Thus, the hydrophobic β-hairpin of RidL is critical for binding of the L. pneumophila effector to the Vps29 retromer subunit and displacement of the regulator TBC1D5.

Intracellular bacterial pathogens subvert the endocytic bactericidal pathway to form specific replication-permissive compartments termed pathogen vacuoles or inclusions. To this end, the pathogens employ type III or type IV secretion systems, which translocate dozens, if not hundreds, of different effector proteins into their host cells, where they manipulate vesicle trafficking and signaling pathways in favor of the intruders. While the distinct cocktail of effectors defines the specific processes by which a pathogen vacuole is formed, the different pathogens commonly target certain vesicle trafficking routes, including the endocytic or secretory pathway. Recently, the retrograde transport pathway from endosomal compartments to the trans-Golgi network emerged as an important route affecting pathogen vacuole formation. Here, we review current insight into the host cell's retrograde trafficking pathway and how vacuolar pathogens of the genera Legionella, Coxiella, Salmonella, Chlamydia, and Simkania employ mechanistically distinct strategies to subvert this pathway, thus promoting intracellular survival and replication., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A nine year old boy who had received Ceftriaxone for one week because of suspected bacterial meningoencephalitis developed colicky abdominal pain in the right upper quadrant two days after termination of Ceftriaxone treatment. Stones in the gallbladder were identified as cause of the abdominal symptoms. Ceftriaxone has been reported to result in so-called pseudo-lithiasis of the gallbladder in approximatively 45% of treated patients, 19% of which developed clinical symptoms. Generally, the gallstones dissolve spontaneously when Ceftriaxone treatment was of short duration.