Critical Care's move to fund open access

SCOPUS: ed.jinfo:eu-repo/semantics/publishe

Role of PknB Kinase in Antibiotic Resistance and Virulence in Community-Acquired Methicillin-Resistant Staphylococcus aureus Strain USA300

The regulation of cellular processes by eukaryote-like serine/threonine kinases is widespread in bacteria. In the last 2 years, several studies have examined the role of serine/threonine kinases in Staphylococcus aureus on cell wall metabolism, autolysis, and virulence, mostly in S. aureus laboratory isolates in the 8325-4 lineage. In this study, we showed that the pknB gene (also called stk1) of methicillin-resistant S. aureus (MRSA) strain COL and the community-acquired MRSA (CA-MRSA) strain USA300 is involved in cell wall metabolism, with the pknB mutant exhibiting enhanced sensitivity to β-lactam antibiotics but not to other classes of antibiotics, including aminoglycosides, ciprofloxacin, bactrim, and other types of cell wall-active agents (e.g., vancomycin and bacitracin). Additionally, the pknB mutant of USA300 was found to be more resistant to Triton X-100-induced autolysis and also to lysis by lysostaphin. We also showed that pknB is a positive regulator of sigB activity, resulting in compromise in its response to heat and oxidative stresses. In association with reduced sigB activity, the expression levels of RNAII and RNAIII of agr and the downstream effector hla are upregulated while spa expression is downmodulated in the pknB mutant compared to the level in the parent. Consistent with an enhanced agr response in vitro, virulence studies of the pknB mutant of USA300 in a murine cutaneous model of infection showed that the mutant was more virulent than the parental strain. Collectively, our results have linked the pknB gene in CA-MRSA to antibiotic resistance, sigB activity, and virulence and have highlighted important differences in pknB phenotypes (virulence and sigB activity) between laboratory isolates and the prototypic CA-MRSA strain USA300

Critical Care: a good scientific citizen just got better

EditorialSCOPUS: ed.jinfo:eu-repo/semantics/publishe

The Surviving Sepsis Campaign: raising awareness to reduce mortality

Sepsis affects 18 million people worldwide every year, and on average each case costs more than US$22 000 to treat. Despite this there is no consensus on the clinical definition of sepsis, and successful diagnosis and treatment is difficult. The Barcelona Declaration, issued by the Surviving Sepsis Campaign in October 2002, outlines a six-point plan to reduce the relative mortality of sepsis by 25% over the next 5 years. The Campaign organizers are currently producing evidence-based guidelines on source control and management of sepsis, as well as a policy document on how sepsis is managed around the world

Detecting Delamination via Nonlinear Wave Scattering in a Bonded Elastic Bar

In this paper we examine the effect of delamination on wave scattering, with the aim of creating a control measure for layered waveguides of various bonding types. Previous works have considered specific widths of solitary waves for the simulations, without analysing the effect of changing the soliton parameters. We consider two multi-layered structures: one containing delamination "sandwiched" by perfect bonding and one containing delamination but "sandwiched" by soft bonding. These structures are modelled by coupled Boussinesq-type equations. Matched asymptotic multiple-scale expansions lead to coupled Ostrovsky equations in soft bonded regions and Korteweg-De Vries equations in the perfectly bonded and delaminated region. We use the Inverse Scattering Transform to predict the behaviour in the delaminated regions. In both cases, numerical analysis shows that we can predict the delamination length by changes in the wave structure, and that these changes depend upon the Full Width at Half Magnitude (FWHM) of the incident soliton. In the case of perfect bonding, we derive a theoretical prediction for the change and confirm this numerically. For the soft bonding case, we numerically identify a similar relationship using the change in amplitude. Therefore we only need to compute one curve to determine the behaviour for any incident solitary wave, creating a framework for designing measurement campaigns for rigorously testing the integrity of layered structures.Comment: 12 pages, 7 figure

Are reviewers suggested by authors as good as those chosen by editors? Results of a rater-blinded, retrospective study

BACKGROUND: BioMed Central (BMC) requires authors to suggest four reviewers when making a submission. Editors searching for reviewers use these suggestions as a source. The review process of the medical journals in the BMC series is open – authors and reviewers know each other's identity – although reviewers can make confidential comments to the editor. Reviews are published alongside accepted articles so readers may see the reviewers' names and recommendations. Our objective was to compare the performance of author-nominated reviewers (ANR) with that of editor-chosen reviewers (ECR) in terms of review quality and recommendations about submissions in an online-only medical journal. METHODS: Pairs of reviews from 100 consecutive submissions to medical journals in the BMC series (with one author-nominated and one editor-chosen reviewer and a final decision) were assessed by two raters, blinded to reviewer type, using a validated review quality instrument (RQI) which rates 7 items on 5-point Likert scales. The raters discussed their ratings after the first 20 pairs (keeping reviewer type masked) and resolved major discrepancies in scoring and interpretation to improve inter-rater reliability. Reviewers' recommendations were also compared. RESULTS: Reviewer source had no impact on review quality (mean RQI score (± SD) 2.24 ± 0.55 for ANR, 2.34 ± 0.54 for ECR) or tone (mean scores on additional question 2.72 ANR vs 2.82 ECR) (maximum score = 5 in both cases). However author-nominated reviewers were significantly more likely to recommend acceptance (47 vs 35) and less likely to recommend rejection (10 vs 23) than editor-chosen reviewers after initial review (p < 0.001). However, by the final review stage (i.e. after authors had responded to reviewer comments) ANR and ECR recommendations were similar (65 vs 66 accept, 10 vs 14 reject, p = 0.47). The number of reviewers unable to decide about acceptance was similar in both groups at both review stages. CONCLUSION: Author-nominated reviewers produced reviews of similar quality to editor-chosen reviewers but were more likely to recommend acceptance during the initial stages of peer review

Introduction of article-processing charges for Population Health Metrics

Population Health Metrics is an open-access online electronic journal published by BioMed Central – it is universally and freely available online to everyone, its authors retain copyright, and it is archived in at least one internationally recognised free repository. To fund this, from November 1 2003, authors of articles accepted for publication will be asked to pay an article-processing charge of US$500. This editorial outlines the reasons for the introduction of article-processing charges and the way in which this policy will work. Waiver requests will be considered on a case-by-case basis, by the Editor-in-Chief. Article-processing charges will not apply to authors whose institutions are 'members' of BioMed Central. Current members include NHS England, the World Health Organization, the US National Institutes of Health, Harvard, Princeton and Yale universities, and all UK universities. No charge is made for articles that are rejected after peer review. Many funding agencies have also realized the importance of open access publishing and have specified that their grants may be used directly to pay APCs

High-Throughput Phenotypic Characterization of Pseudomonas aeruginosa Membrane Transport Genes

The deluge of data generated by genome sequencing has led to an increasing reliance on bioinformatic predictions, since the traditional experimental approach of characterizing gene function one at a time cannot possibly keep pace with the sequence-based discovery of novel genes. We have utilized Biolog phenotype MicroArrays to identify phenotypes of gene knockout mutants in the opportunistic pathogen and versatile soil bacterium Pseudomonas aeruginosa in a relatively high-throughput fashion. Seventy-eight P. aeruginosa mutants defective in predicted sugar and amino acid membrane transporter genes were screened and clear phenotypes were identified for 27 of these. In all cases, these phenotypes were confirmed by independent growth assays on minimal media. Using qRT-PCR, we demonstrate that the expression levels of 11 of these transporter genes were induced from 4- to 90-fold by their substrates identified via phenotype analysis. Overall, the experimental data showed the bioinformatic predictions to be largely correct in 22 out of 27 cases, and led to the identification of novel transporter genes and a potentially new histamine catabolic pathway. Thus, rapid phenotype identification assays are an invaluable tool for confirming and extending bioinformatic predictions

Substrate Specificity within a Family of Outer Membrane Carboxylate Channels

Characterization of a large family of outer membrane channels from gram-negative bacteria suggest how they can thrive in nutrient-poor environments and how channel inactivation can contribute to antibiotic resistance

Whole Genome Sequencing and Complete Genetic Analysis Reveals Novel Pathways to Glycopeptide Resistance in Staphylococcus aureus

The precise mechanisms leading to the emergence of low-level glycopeptide resistance in Staphylococcus aureus are poorly understood. In this study, we used whole genome deep sequencing to detect differences between two isogenic strains: a parental strain and a stable derivative selected stepwise for survival on 4 µg/ml teicoplanin, but which grows at higher drug concentrations (MIC 8 µg/ml). We uncovered only three single nucleotide changes in the selected strain. Nonsense mutations occurred in stp1, encoding a serine/threonine phosphatase, and in yjbH, encoding a post-transcriptional negative regulator of the redox/thiol stress sensor and global transcriptional regulator, Spx. A missense mutation (G45R) occurred in the histidine kinase sensor of cell wall stress, VraS. Using genetic methods, all single, pairwise combinations, and a fully reconstructed triple mutant were evaluated for their contribution to low-level glycopeptide resistance. We found a synergistic cooperation between dual phospho-signalling systems and a subtle contribution from YjbH, suggesting the activation of oxidative stress defences via Spx. To our knowledge, this is the first genetic demonstration of multiple sensor and stress pathways contributing simultaneously to glycopeptide resistance development. The multifactorial nature of glycopeptide resistance in this strain suggests a complex reprogramming of cell physiology to survive in the face of drug challenge