Observatoire régional du pneumocoque en région Pays de la Loire : résistance de Streptococcus pneumoniae aux antibiotiques en 2007

But de l’étudeEntre le 1er janvier et le 31 décembre 2007, les 20 laboratoires participant à l’observatoire régional du pneumocoque (ORP) Pays de la Loire ont collecté 331 souches invasives de Streptococcus pneumoniae afin d’étudier leur sensibilité aux antibiotiques et la répartition des sérogroupes/sérotypes. Méthode Les concentrations minimales inhibitrices (CMI) de la pénicilline G, de l’amoxicilline et du céfotaxime ont été déterminées par le centre coordinateur, par la méthode de référence de diffusion en milieu gélosé. Les résultats ont été interprétés selon les recommandations du CA-SFM. Les sensibilités à d’autres antibiotiques ont été étudiées et les typages des souches réalisées par le centre coordinateur. Résultats Trois cent trente et une souches ont été isolées en 2007. Elles provenaient de 30 liquides céphalorachidiens, 239 hémocultures, 53 pus d’otites moyennes aiguës et neuf liquides pleuraux. Le pourcentage de pneumocoques de sensibilité diminuée à la pénicilline G (PSDP) était de 39 % et restait plus élevé chez l’enfant (51 %) que chez l’adulte (35 %). Les PSDP étaient souvent multirésistants, avec en particulier un pourcentage élevé de résistance à l’érythromycine (87,6 % contre 8,4 % pour les pneumocoques sensibles à la pénicilline). Enfin, le sérogroupe majoritairement rencontré était le sérogroupe 19 (29,6 % des isolats). Conclusion Une diminution des PSDP a été observée depuis 2001 et les souches de haut niveau de résistance aux β-lactamines restent rares. Le pourcentage de PSDP observés en ORP Pays de la Loire demeure dans la moyenne nationale

Observatoire Régional du Pneumocoque en région Pays de la Loire : résistance de Streptococcus pneumoniae (Sp) aux antibiotiques en 2007

Date du colloque&nbsp;: 12/2008</p

Analysis of SEC9 Suppression Reveals a Relationship of SNARE Function to Cell Physiology

BACKGROUND:Growth and division of Saccharomyces cerevisiae is dependent on the action of SNARE proteins that are required for membrane fusion. SNAREs are regulated, through a poorly understood mechanism, to ensure membrane fusion at the correct time and place within a cell. Although fusion of secretory vesicles with the plasma membrane is important for yeast cell growth, the relationship between exocytic SNAREs and cell physiology has not been established. METHODOLOGY/PRINCIPAL FINDINGS:Using genetic analysis, we identified several influences on the function of exocytic SNAREs. Genetic disruption of the V-ATPase, but not vacuolar proteolysis, can suppress two different temperature-sensitive mutations in SEC9. Suppression is unlikely due to increased SNARE complex formation because increasing SNARE complex formation, through overexpression of SRO7, does not result in suppression. We also observed suppression of sec9 mutations by growth on alkaline media or on a non-fermentable carbon source, conditions associated with a reduced growth rate of wild-type cells and decreased SNARE complex formation. CONCLUSIONS/SIGNIFICANCE:Three main conclusions arise from our results. First, there is a genetic interaction between SEC9 and the V-ATPase, although it is unlikely that this interaction has functional significance with respect to membrane fusion or SNAREs. Second, Sro7p acts to promote SNARE complex formation. Finally, Sec9p function and SNARE complex formation are tightly coupled to the physiological state of the cell

A Novel Function of Noc2 in Agonist-Induced Intracellular Ca2+ Increase during Zymogen-Granule Exocytosis in Pancreatic Acinar Cells

Noc2, a putative Rab effector, contributes to secretory-granule exocytosis in neuroendocrine and exocrine cells. Here, using two-photon excitation live-cell imaging, we investigated its role in Ca2+-dependent zymogen granule (ZG) exocytosis in pancreatic acinar cells from wild-type (WT) and Noc2-knockout (KO) mice. Imaging of a KO acinar cell revealed an expanded granular area, indicating ZG accumulation. In our spatiotemporal analysis of the ZG exocytosis induced by agonist (cholecystokinin or acetylcholine) stimulation, the location and rate of progress of ZG exocytosis did not differ significantly between the two strains. ZG exocytosis from KO acinar cells was seldom observed at physiological concentrations of agonists, but was normal (vs. WT) at high concentrations. Flash photolysis of a caged calcium compound confirmed the integrity of the fusion step of ZG exocytosis in KO acinar cells. The decreased ZG exocytosis present at physiological concentrations of agonists raised the possibility of impaired elicitation of calcium spikes. When calcium spikes were evoked in KO acinar cells by a high agonist concentration: (a) they always started at the apical portion and traveled to the basal portion, and (b) calcium oscillations over the 10 µM level were observed, as in WT acinar cells. At physiological concentrations of agonists, however, sufficient calcium spikes were not observed, suggesting an impaired [Ca2+]i-increase mechanism in KO acinar cells. We propose that in pancreatic acinar cells, Noc2 is not indispensable for the membrane fusion of ZG per se, but instead performs a novel function favoring agonist-induced physiological [Ca2+]i increases

The GTPase RalA Regulates Different Steps of the Secretory Process in Pancreatic β-Cells

BACKGROUND: RalA and RalB are multifuntional GTPases involved in a variety of cellular processes including proliferation, oncogenic transformation and membrane trafficking. Here we investigated the mechanisms leading to activation of Ral proteins in pancreatic beta-cells and analyzed the impact on different steps of the insulin-secretory process. METHODOLOGY/PRINCIPAL FINDINGS: We found that RalA is the predominant isoform expressed in pancreatic islets and insulin-secreting cell lines. Silencing of this GTPase in INS-1E cells by RNA interference led to a decrease in secretagogue-induced insulin release. Real-time measurements by fluorescence resonance energy transfer revealed that RalA activation in response to secretagogues occurs within 3-5 min and reaches a plateau after 10-15 min. The activation of the GTPase is triggered by increases in intracellular Ca2+ and cAMP and is prevented by the L-type voltage-gated Ca2+ channel blocker Nifedipine and by the protein kinase A inhibitor H89. Defective insulin release in cells lacking RalA is associated with a decrease in the secretory granules docked at the plasma membrane detected by Total Internal Reflection Fluorescence microscopy and with a strong impairment in Phospholipase D1 activation in response to secretagogues. RalA was found to be activated by RalGDS and to be severely hampered upon silencing of this GDP/GTP exchange factor. Accordingly, INS-1E cells lacking RalGDS displayed a reduction in hormone secretion induced by secretagogues and in the number of insulin-containing granules docked at the plasma membrane. CONCLUSIONS/SIGNIFICANCE: Taken together, our data indicate that RalA activation elicited by the exchange factor RalGDS in response to a rise in intracellular Ca2+ and cAMP controls hormone release from pancreatic beta-cell by coordinating the execution of different events in the secretory pathway

Synthesis of acyclic nucleoside phosphonates as potent antimalarials

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