Hospital Son Dureta IUNICS

Palma, Spain

Hospital Son Dureta IUNICS

Palma, Spain

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Couce A.,CSIC - National Center for Biotechnology | Couce A.,French Institute of Health and Medical Research | Alonso-Rodriguez N.,CSIC - National Center for Biotechnology | Alonso-Rodriguez N.,Institute Pasteur Paris | And 5 more authors.
Clinical Microbiology and Infection | Year: 2016

Bacteria with elevated mutation rates represent a risk factor for treatment failure and are often found with high frequency in clinical isolates from different sources. How this frequency reflects the among-population and within-population proportion of hypermutators is unknown, despite its importance to the choice of antibiotic therapies that minimize the likelihood of resistance development. Here we screened for hypermutators among the urine of 80 patients with urinary tract infections, at an unprecedented resolution of 24 isolates per sample. We found hypermutators in four patients (5%), at frequencies ranging from 4.2% to 62.5%. Molecular characterization revealed alterations in the oxidized guanine (GO) and methly-directed mistmatch repair (MMR) systems and the mismatch repair system as the genetic basis of hypermutability. These observations suggest that mutators may be present in more patients than previously anticipated, at frequencies that are difficult to detect but still sufficient to impact on adaptation to antibiotics or the host environment. © 2016 European Society of Clinical Microbiology and Infectious Diseases.


Costas J.,Hospital Clinico Universitario | Gratacos M.,CIBER ISCIII | Escaramis G.,CIBER ISCIII | Martin-Santos R.,IMIM Hospital del Mar and Hospital Clinico | And 17 more authors.
Journal of Psychiatric Research | Year: 2010

The post-partum period is a time of extreme vulnerability for a whole spectrum of psychiatric disorders. Delivery may be considered an important risk factor in genetically susceptible women. Five hundred and eight SNPs in 44 genes at candidate pathways putatively related to mood changes after delivery were genotyped in a multicenter cohort of 1804 women from Spain. Participants completed two scales at 2-3. days, 8. weeks, and 32. weeks post-partum, the Edinburgh Post-partum Depression Scale (EPDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Those women who scored 9 or more on EPDS were evaluated for major depression using the Diagnostic Interview for Genetics Studies (DIGS) adapted for post-partum depression. Association with major depression was assessed using likelihood ratio tests under a codominant genotype model. Association with scale scores was tested using linear mixed models to take into account repeated measures over time. Two intronic SNPs, one at the serotonin transporter gene (SLC6A4) and another at dopa decarboxylase (DDC), were significantly associated to STAI anxiety scores after multiple testing correction (nominal P=0.0000513 and 0.000097, respectively). In addition, post hoc analysis at the unphased haplotype level using nominal significant SNPs revealed an association with a combination of three SNPs at protein kinase C, beta (PRKCB) with major depression, significant after multiple testing correction (nominal global P=0.0001596). In conclusion, we detected a role of SLC6A4 in mood changes after stressful events, and revealed new putative associations involving DDC and PRKCB. Therefore, these genes deserve further investigation to confirm these results. © 2009 Elsevier Ltd.


PubMed | Hospital Son Dureta IUNICS and CSIC - National Center for Biotechnology
Type: Journal Article | Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases | Year: 2016

Bacteria with elevated mutation rates represent a risk factor for treatment failure and are often found with high frequency in clinical isolates from different sources. How this frequency reflects the among-population and within-population proportion of hypermutators is unknown, despite its importance to the choice of antibiotic therapies that minimize the likelihood of resistance development. Here we screened for hypermutators among the urine of 80 patients with urinary tract infections, at an unprecedented resolution of 24 isolates per sample. We found hypermutators in four patients (5%), at frequencies ranging from 4.2% to 62.5%. Molecular characterization revealed alterations in the oxidized guanine (GO) and methly-directed mistmatch repair (MMR) systems as the genetic basis of hypermutability. These observations suggest that mutators may be present in more patients than previously anticipated, at frequencies that are difficult to detect but still sufficient to impact on adaptation to antibiotics or the host environment.

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