Changes in urine composition after trauma facilitate bacterial growth.

International audienceUNLABELLED: ABSTRACT: BACKGROUND: Critically ill patients including trauma patients are at high risk of urinary tract infection (UTI). The composition of urine in trauma patients may be modified due to inflammation, systemic stress, rhabdomyolysis, life support treatment and/or urinary catheter insertion. METHODS: Prospective, single-centre, observational study conducted in patients with severe trauma and without a history of UTIs or recent antibiotic treatment. The 24-hour urine samples were collected on the first and the fifth days and the growth of Escherichia coli in urine from patients and healthy volunteers was compared. Biochemical and hormonal modifications in urine that could potentially influence bacterial growth were explored. RESULTS: Growth of E. coli in urine from trauma patients was significantly higher on days 1 and 5 than in urine of healthy volunteers. Several significant modifications of urine composition could explain these findings. On days 1 and 5, trauma patients had an increase in glycosuria, in urine iron concentration, and in the concentrations of several amino acids compared to healthy volunteers. On day 1, the urinary osmotic pressure was significantly lower than for healthy volunteers. CONCLUSION: We showed that urine of trauma patients facilitated growth of E. coli when compared to urine from healthy volunteers. This effect was present in the first 24 hours and until at least the fifth day after trauma. This phenomenon may be involved in the pathophysiology of UTIs in trauma patients. Further studies are required to define the exact causes of such modifications

Frontières. Actes du colloque québéco-norvégien

D’emblée, la notion de « frontière » met de l’avant les découpages, les définitions, les limites. Elle est ainsi foncièrement pluridisciplinaire, voire métadisciplinaire. Comme la notion elle-même, la collaboration en études littéraires entre le Québec et la Norvège à la source de ce livre s’ancre dans une dimension territoriale et géopolitique, mais ouvre sur les enjeux qui en découlent. C’est ainsi beaucoup plus largement une réflexion sur les consensus et les interférences entre différents champs disciplinaires que le lecteur trouvera dans les chapitres qui composent cet ouvrage. À la fois fondatrice et arbitraire, la frontière s’avère un point d’observation fertile des circulations et des carrefours, une notion clé dont l’actualité ne cesse de marteler l’importance, et qu’il faut repenser dans ses dimensions concrètes mais aussi symboliques pour aborder l’imaginaire contemporain

Organised Genome Dynamics in the Escherichia coli Species Results in Highly Diverse Adaptive Paths

The Escherichia coli species represents one of the best-studied model organisms, but also encompasses a variety of commensal and pathogenic strains that diversify by high rates of genetic change. We uniformly (re-) annotated the genomes of 20 commensal and pathogenic E. coli strains and one strain of E. fergusonii (the closest E. coli related species), including seven that we sequenced to completion. Within the ∼18,000 families of orthologous genes, we found ∼2,000 common to all strains. Although recombination rates are much higher than mutation rates, we show, both theoretically and using phylogenetic inference, that this does not obscure the phylogenetic signal, which places the B2 phylogenetic group and one group D strain at the basal position. Based on this phylogeny, we inferred past evolutionary events of gain and loss of genes, identifying functional classes under opposite selection pressures. We found an important adaptive role for metabolism diversification within group B2 and Shigella strains, but identified few or no extraintestinal virulence-specific genes, which could render difficult the development of a vaccine against extraintestinal infections. Genome flux in E. coli is confined to a small number of conserved positions in the chromosome, which most often are not associated with integrases or tRNA genes. Core genes flanking some of these regions show higher rates of recombination, suggesting that a gene, once acquired by a strain, spreads within the species by homologous recombination at the flanking genes. Finally, the genome's long-scale structure of recombination indicates lower recombination rates, but not higher mutation rates, at the terminus of replication. The ensuing effect of background selection and biased gene conversion may thus explain why this region is A+T-rich and shows high sequence divergence but low sequence polymorphism. Overall, despite a very high gene flow, genes co-exist in an organised genome

Molecular and Evolutionary Bases of Within-Patient Genotypic and Phenotypic Diversity in Escherichia coli Extraintestinal Infections

Although polymicrobial infections, caused by combinations of viruses, bacteria, fungi and parasites, are being recognised with increasing frequency, little is known about the occurrence of within-species diversity in bacterial infections and the molecular and evolutionary bases of this diversity. We used multiple approaches to study the genomic and phenotypic diversity among 226 Escherichia coli isolates from deep and closed visceral infections occurring in 19 patients. We observed genomic variability among isolates from the same site within 11 patients. This diversity was of two types, as patients were infected either by several distinct E. coli clones (4 patients) or by members of a single clone that exhibit micro-heterogeneity (11 patients); both types of diversity were present in 4 patients. A surprisingly wide continuum of antibiotic resistance, outer membrane permeability, growth rate, stress resistance, red dry and rough morphotype characteristics and virulence properties were present within the isolates of single clones in 8 of the 11 patients showing genomic micro-heterogeneity. Many of the observed phenotypic differences within clones affected the trade-off between self-preservation and nutritional competence (SPANC). We showed in 3 patients that this phenotypic variability was associated with distinct levels of RpoS in co-existing isolates. Genome mutational analysis and global proteomic comparisons in isolates from a patient revealed a star-like relationship of changes amongst clonally diverging isolates. A mathematical model demonstrated that multiple genotypes with distinct RpoS levels can co-exist as a result of the SPANC trade-off. In the cases involving infection by a single clone, we present several lines of evidence to suggest diversification during the infectious process rather than an infection by multiple isolates exhibiting a micro-heterogeneity. Our results suggest that bacteria are subject to trade-offs during an infectious process and that the observed diversity resembled results obtained in experimental evolution studies. Whatever the mechanisms leading to diversity, our results have strong medical implications in terms of the need for more extensive isolate testing before deciding on antibiotic therapies

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

Correction to: Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.

After publication of the original article [1], we were notified that columns in Table 2 were erroneously displayed

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] ¼ 0.99, 95% confidence interval [CI] ¼ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc¼ 0.79, 95% CI ¼ 0.69 to 0.91; HRc¼ 0.70, 95% CI ¼ 0.59 to 0.82; HRc¼ 0.50, 95% CI ¼ 0.40 to 0.63, for 2, 3, and 4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend ¼ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] ¼ 1.69, 95% CI ¼ 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc ¼ 1.33, 95% CI ¼ 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc¼ 0.72, 95% CI ¼ 0.54 to 0.98). Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

Voies d'entree du glucose chez les Enterobacteries

CNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Diversité métabolique au sein de l'espèce Escherichia coli (implications dans les capacités d'adaptation et la virulence)

Nous effectuons une étude de la diversité métabolique de divers isolais de E. coli afin (i) d'établir un lien entre métabolisme et virulence et, (ii) de mieux comprendre la physiopathologie des infections urinaires (IU). Les activités enzymatiques spécifiques d'enzymes du métabolisme central sont mesurées à la phase exponentielle dans 4 milieux pour 5 souches. Une diversité intra espèce du métabolisme et des capacités d'adaptation est mise en évidence. Elle peut être rattachée au phénotype pathogène ou commensal et à la niche. E. coli CFT073, uropathogène, favorise le métabolisme de l'acétate et les voies de biosynthèse dans l'urine. L'évaluation de l'homéostasie redox de 8 souches montre que la phase exponentielle, par rapport à la phase stationnaire de la croissance dans l'urine, est associée à un déséquilibre de l'homéostasie redox. Un stress systémique modifie la composition de l'urine, favorisant la croissance de E. coli qui pourrait participer à la survenue d'IU en réanimation.We carry out a study of the metabolic diversity for some strains of E. coli, in order to (i) point out a link between metabolism and virulence and, (ii) improve our understanding of urinary tract infections (UTI). The specific activity of some enzymes from the central metabolism was measured for 5 strains yielded in 4 mediums. We highlight a metabolic diversity, which could be linked to strain's habitats or pathovars. The uropathogenic strain, E. coli CFT073, favours acetate metabolism and neoglucogenesis during growth in urine. The study of redox homeostasis for 8 E. coli strains shows an unbalance during exponential phase by comparison with stationary phase. A systemic stress, such as a polytraumatism, is responsible for changes in urine composition, which could be a risk factor of UTI occurrence in unwell intensive care patients.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

Diversité métabolique liée à la synthèse de polyhydroxyalcanoates chez les Pseudomonas

Les polyhydroxyalcanoates (PHA) sont des polyesters produits par de nombreuses bactéries sous forme d'inclusions cytoplasmiques. Les propriétés de biocomptabilité et de biodégradabilité de ces biopolymères permettent d'envisager de nombreuses applications dans le domaine médical. La majorité des polymères produits par les bactéries sont des ssc-PHAs (short-side-chain-PHAs). Les msc-PHAs (medium-side-chain-PHAs) quant à eux ne sont retrouvés qu'au sein du genre bactérien des Pseudomonas. Dans notre première étude, nous nous intéressé à la diversité des PHAs synthétisés par les Pseudomonas. Nous avons montré que ce genre bactérien n'est pas homogène au regard de la synthèse de polymère. En effet, nous avons identifié un cluster produisant un ssc-PHA. A partir de ce travail, nous avons sélectionné certaines espèces bactériennes pour leur fort potentiel d'accumulation de polymère. Le comportement de ces souches dans différentes conditions environnementales a été l'objet de la deuxième étude. A travers les quelques souches étudiées qui sont pourtant toute proche phylogénétiquement, nous avons montré des disparités dans l'accumulation de polymère par les bactéries. Nous avons pu constater que la bactérie Pseudomonas putida bv B présente un profil très particulier vis-à-vis du valérate qui est un acide gras possédant un fort pouvoir bactériostatique. Le polymère synthétisé par cette bactérie à partir de cette seule source de carbone est très hétérogène et révèle un mécanisme de synthèse original protégeant la bactérie de la toxicité du valérate. Dans un but de valorisation, nous avons également synthétisé un nouveau polymère présentant des instaurations dans la chaîne latérale. Ce matériau peut ainsi subir des modifications chimiques telles que le greffage ou la réticulation. Il constitue ainsi une matrice évolutive dont les propriétés pourraient être adaptées au cahier des charges de la nanoencapsulation et de la vestorisation de principes actifs.PARIS12-CRETEIL BU Multidisc. (940282102) / SudocSudocFranceF