Genomic analysis of an emerging multiresistant Staphylococcus aureus strain rapidly spreading in cystic fibrosis patients revealed the presence of an antibiotic inducible bacteriophage

BACKGROUND: Staphylococcus aureus is a major human pathogen responsible for a variety of nosocomial and community-acquired infections. Recent reports show that the prevalence of Methicillin-Resistant S. aureus (MRSA) infections in cystic fibrosis (CF) patients is increasing. In 2006 in Marseille, France, we have detected an atypical MRSA strain with a specific antibiotic susceptibility profile and a unique growth phenotype. Because of the clinical importance of the spread of such strain among CF patients we decided to sequence the genome of one representative isolate (strain CF-Marseille) to compare this to the published genome sequences. We also conducted a retrospective epidemiological analysis on all S. aureus isolated from 2002 to 2007 in CF patients from our institution. RESULTS: CF-Marseille is multidrug resistant, has a hetero-Glycopeptide-Intermediate resistance S. aureus phenotype, grows on Cepacia agar with intense orange pigmentation and has a thickened cell wall. Phylogenetic analyses using Complete Genome Hybridization and Multi Locus VNTR Assay showed that CF-Marseille was closely related to strain Mu50, representing vancomycin-resistant S. aureus. Analysis of CF-Marseille shows a similar core genome to that of previously sequenced MRSA strains but with a different genomic organization due to the presence of specific mobile genetic elements i.e. a new SCCmec type IV mosaic cassette that has integrated the pUB110 plasmid, and a new phage closely related to phiETA3. Moreover this phage could be seen by electron microscopy when mobilized with several antibiotics commonly used in CF patients including, tobramycin, ciprofloxacin, cotrimoxazole, or imipenem. Phylogenetic analysis of phenotypically similar h-GISA in our study also suggests that CF patients are colonized by polyclonal populations of MRSA that represents an incredible reservoir for lateral gene transfer. CONCLUSION: In conclusion, we demonstrated the emergence and spreading of a new isolate of MRSA in CF patients in Marseille, France, that has probably been selected in the airways by antibiotic pressure. Antibiotic-mediated phage induction may result in high-frequency transfer and the unintended consequence of promoting the spread of virulence and/or antibiotic resistance determinants. The emergence of well-adapted MRSA is worrying in such population chronically colonized and receiving many antibiotics and represents a model for emergence of uncontrollable super bugs in a specific niche. REVIEWERS: This article was reviewed by Eric Bapteste, Pierre Pontarotti, and Igor Zhulin. For the full reviews, please go to the Reviewers' comments section

PLoS Pathog

Cytomegalovirus (CMV) is a leading infectious cause of morbidity in immune-compromised patients. γδ T cells have been involved in the response to CMV but their role in protection has not been firmly established and their dependency on other lymphocytes has not been addressed. Using C57BL/6 αβ and/or γδ T cell-deficient mice, we here show that γδ T cells are as competent as αβ T cells to protect mice from CMV-induced death. γδ T cell-mediated protection involved control of viral load and prevented organ damage. γδ T cell recovery by bone marrow transplant or adoptive transfer experiments rescued CD3ε-/- mice from CMV-induced death confirming the protective antiviral role of γδ T cells. As observed in humans, different γδ T cell subsets were induced upon CMV challenge, which differentiated into effector memory cells. This response was observed in the liver and lungs and implicated both CD27+ and CD27- γδ T cells. NK cells were the largely preponderant producers of IFNγ and cytotoxic granules throughout the infection, suggesting that the protective role of γδ T cells did not principally rely on either of these two functions. Finally, γδ T cells were strikingly sufficient to fully protect Rag-/-γc-/- mice from death, demonstrating that they can act in the absence of B and NK cells. Altogether our results uncover an autonomous protective antiviral function of γδ T cells, and open new perspectives for the characterization of a non classical mode of action which should foster the design of new γδ T cell based therapies, especially useful in αβ T cell compromised patients

Les organisations et leurs marchés du travail: Une comparaison du monde musical et du monde universitaire

Organizations and labour markets.A comparison of the academic and musical worldsBuilding on a comparison of the academic and musical worlds, this paper explores a classical issue in the sociology of organizations, i.e. the relationships between an organization and its environment, by focusing on the labor markets on which organizations intervene. It reveals three different types of articulation between organizations and their labor markets: a first one where ephemeral organizations are linked to labor markets of spot contracts; a second one where quasi-firms rely on labor markets of time-limited but renewable contracts, and a third one where permanent organizations build a labor market of tenured positions. The authors conclude that the links that develop between an organization and its environment first of all depend on the very nature of the type work achieved within this organization.En s’appuyant sur une comparaison des secteurs musical et universitaire, l’article revient sur une question classique de sociologie des organisations, celle des liens qui s’établissent entre une organisation et son environnement, en s’intéressant plus particulièrement au marché du travail sur lequel elle intervient. L’article met au jour trois modalités d’articulation des organisations et de leurs marchés du travail : les organisations éphémères adossées à des marchés pour des contrats de travail ponctuels ; les quasi-firmes appuyées sur des marchés du travail pour des emplois éphémères mais reconductibles ; les organisations permanentes articulées aux marchés du travail des emplois à durée indéterminée. Il montre que les liens de détermination qui s’établissent entre l’organisation et son environnement dépendent avant tout de la nature du travail qu’abrite l’organisation

L'anxiété et la dépression liées à la fin de vie soulagées par psychothérapie assistée de psychédéliques

International audienceLa personne confrontée à la mort peut avoir des besoins psychologiques et spirituels qui nécessitent une prise en charge globale. Actuellement, les psychothérapies et pharmacothérapies proposées en soins palliatifs montrent seulement des effets faibles à modérés sur la qualité de vie, l’anxiété et la dépression des patients. Cet article expose comment la réintroduction d’une prise en charge alternative, la psychothérapie assistée par psychédéliques, pourrait permettre aux patients à la fois de mieux accepter l’idée de la mort et de se sentir plus satisfaits envers la vie en général. Nous présentons les résultats des essais cliniques menés jusqu’à aujourd’hui et détaillons quels phénomènes psychologiques pourraient être à l’origine des effets psychothérapeutiques de l’expérience psychédélique. Les propos sont illustrés par le témoignage d’un patient atteint de cancer ayant vécu une expérience psychédélique en milieu naturel avec de l’acide lysergique diéthylamide. La manière dont est administrée la psychothérapie assistée par psychédéliques et ses spécificités par rapport aux traitements classiques sont également abordées. Nous concluons en proposant que la réintroduction des psychothérapies assistées par psychédéliques en soins palliatifs, en plus d’améliorer la prise en charge des patients, pourrait faire évoluer le rapport à la mort dans la société

A large-volume low-pressure nasal irrigation delivers drug into the nasal cavity? An in vivo study

International audienc

A large-volume low-pressure nasal irrigation delivers drug into the nasal cavity? An in vivo study.

The nasal administration route emerged as an interesting route in systemic and brain drug delivery, and different modalities of nasal delivery are available. The nasal irrigation is one of them, but there is a lack of studies investigating the distribution of a large-volume irrigation. The main aim of this study was to assess the deposition of radiolabeled saline in the nasal cavities and paranasal sinuses following nasal irrigation by imaging. Five healthy males volunteered to perform large-volume low-pressure nasal irrigation, with a douching device containing 50 mL of radiolabeled isotonic saline. Participants underwent a scintigraphy immediately after. Both the nasal cavities and maxillary sinuses were systematically reached by the solution during nasal irrigation. The sinuses set in a lower position during nasal irrigation showed a tendency to be more irrigated than the sinuses set in a higher position (7.67% vs 22.72%; p = 0.086). Moreover, substantial inter- and intraindividual heterogeneity regarding solution deposition was observed. Large-volume low-pressure nasal irrigation is a good modality to reach the maxillary sinuses as well as the nasal cavities. In order to ensure adequate reaching of both nasal cavities and paranasal sinuses, nasal irrigation should be performed bilaterally

Image Quality Analysis of Photon-Counting CT Compared with Dual-Source CT: A Phantom Study for Chest CT Examinations

A comparison was made between the image quality of a photon-counting CT (PCCT) and a dual-source CT (DSCT). The evaluation of image quality was performed using a Catphan CT phantom, and the physical metrics, such as the noise power spectrum and task transfer function, were measured for both PCCT and DSCT at three CT dose indices (1, 5 and 10 mGy). Polyenergetic and virtual monoenergetic reconstructions were used to evaluate the performance differences by simulating a Gaussian spot with a radius of 5 mm and calculating the detectability index. The highest iterative reconstruction level was able to decrease the noise by about 70% compared with the filtered back projection using a parenchyma reconstruction kernel. The PCCT task transfer functions remained constant, while those of the DSCT increased with the reconstruction strength level. At monoenergetic 70 keV, a 50% decrease in noise was observed for DSCT with image smoothing, while PCCT had the same 50% decrease in noise without any smoothing. The PCCT detectability index at a reconstruction strength level of two was equivalent to the highest level of ADMIRE 5 for DSCT. The PCCT showed its superiority over the DSCT, especially for lung nodule detection