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Unlabelled: Legionella pneumophila, the etiological agent of legionellosis, replicates within phagocytic cells. Crucial to biogenesis of the replicative vacuole is the Dot/Icm type 4 secretion system, which translocates a large number of effectors into the host cell cytosol. Among them is LegK2, a protein kinase that plays a key role in Legionella infection. Here, we identified the actin nucleator ARP2/3 complex as a target of LegK2. LegK2 phosphorylates the ARPC1B and ARP3 subunits of the ARP2/3 complex. LegK2-dependent ARP2/3 phosphorylation triggers global actin cytoskeleton remodeling in cells, and it impairs actin tail formation by Listeria monocytogenes, a well-known ARP2/3-dependent process. During infection, LegK2 is addressed to the Legionella-containing vacuole surface and inhibits actin polymerization on the phagosome, as revealed by legK2 gene inactivation. Consequently, LegK2 prevents late endosome/lysosome association with the phagosome and finally contributes to remodeling of the bacterium-containing phagosome into a replicative niche. The inhibition of actin polymerization by LegK2 and its effect on endosome trafficking are ARP2/3 dependent since it can be phenocopied by a specific chemical inhibitor of the ARP2/3 complex. Thus, LegK2-ARP2/3 interplay highlights an original mechanism of bacterial virulence with an unexpected role in local actin remodeling that allows bacteria to control vesicle trafficking in order to escape host defenses., Importance: Deciphering the individual contribution of each Dot/Icm type 4 secretion system substrate to the intracellular life-style of L. pneumophila remains the principal challenge in understanding the molecular basis of Legionella virulence. Our finding that LegK2 is a Dot/Icm effector that inhibits actin polymerization on the Legionella-containing vacuole importantly contributes to the deciphering of the molecular mechanisms evolved by Legionella to counteract the endocytic pathway. Indeed, our results highlight the essential role of LegK2 in preventing late endosomes from fusing with the phagosome. More generally, this work is the first demonstration of local actin remodeling as a mechanism used by bacteria to control organelle trafficking. Further, by characterizing the role of the bacterial protein kinase LegK2, we reinforce the concept that posttranslational modifications are key strategies used by pathogens to evade host cell defenses., (Copyright © 2015 Michard et al.)

Legionella pneumophila is the etiological agent of Legionnaires' disease. Crucial to the pathogenesis of this intracellular pathogen is its ability to subvert host cell defenses, permitting intracellular replication in specialized vacuoles within host cells. The Dot/Icm type IV secretion system (T4SS), which translocates a large number of bacterial effectors into host cell, is absolutely required for rerouting the Legionella phagosome. Many Legionella effectors display distinctive eukaryotic domains, among which are protein kinase domains. In silico analysis and in vitro phosphorylation assays identified five functional protein kinases, LegK1 to LegK5, encoded by the epidemic L. pneumophila Lens strain. Except for LegK5, the Legionella protein kinases are all T4SS effectors. LegK2 plays a key role in bacterial virulence, as demonstrated by gene inactivation. The legK2 mutant containing vacuoles displays less-efficient recruitment of endoplasmic reticulum markers, which results in delayed intracellular replication. Considering that a kinase-dead substitution mutant of legK2 exhibits the same virulence defects, we highlight here a new molecular mechanism, namely, protein phosphorylation, developed by L. pneumophila to establish a replicative niche and evade host cell defenses.

The authors report 189 case histories of pregnant women who had a neurological disorder, which either existed before the pregnancy or were discovered during the pregnancy. The most frequent aetiological conditions were, epilepsy, psychoses, vascular accidents, tumours and disseminated sclerosis. Pregnancy and neuropathology are an association for which the prognosis as a whole is good and linked to the time in the pregnancy when the neurological condition, whether it is stable or not, is discovered. The combination is absolutely compatible with the normal progress of pregnancy so long as the appropriate treatment is continued during the pregnancy. Cerebral vascular accidents that occur in pregnancy make the prognosis very much worse. In these circumstances neurosurgery may give some hope. This applies also for cerebral tumours, among which pituitary adenoma is becoming more and more frequent. Psychopathies can be a very baffling chapter when they are combined with pregnancy. Finally disseminated sclerosis, once it has been stabilised, is perfectly compatible with the normal outcome for a pregnancy.

A personal case which has been studied has given the authors the opportunity of analysing the characteristics of clear-cell adenocarcinoma of the vagina in a young girl. Adhesions are most often discovered in cases of metrorrhagia or discharge about the time of puberty. Thence as a friable tumour on the anterior wall of the vagina. Usually diethylstilboestrol has been given during intrauterine life. Histologically clear cell carcinomata of the vagina are characterised by a glandular structure in which large cells with large nuclei and clear cytoplasm as well as small cells with "tapestry-maker nail patterns" are found together. Treatment is surgical: total colpohysterectomy with conservation of the ovaries, with lymphadenectomy and with conservation of a vaginal cavity. Prevention consists in screening those who have been exposed to the risk and treating lesions that have been found, but above all in care in using estrogens in pregnant women.

The authors report a case of amenorrhoea with galatorrheoa due to a prolactin adenoma secondary to an inducer of ovulation (HMG and HCG) and in which pregnancy occurred. There was sudden progression of the adenoma with formation of a haematoma and the necessity for emergency surgery. In the light of this case, the risks and indications of inducers of ovulation in the sterile woman complaining of amenorrhoea with galactorrhoea are discussed.