Eradication of methicillin-resistant Staphylococcus aureus with an antiseptic soap and nasal mupirocin among colonized patients – an open uncontrolled clinical trial

BACKGROUND: Aim of the study was to determine the clinical efficacy of a new antiseptic liquid soap (Stellisept(® )scrub), based on the combination of undecylenamidopropyltrimonium methosulphate (4%) and phenoxyethanol (2%), for eradication of MRSA among colonized patients who do not receive antibiotic therapy. METHODS: Over two years 50 MRSA patients in 6 hospitals were observed. Treatment was defined as the daily application of Stellisept scrub for the antiseptic body and hair wash (at least 60 s) in combination with nasal mupirocin. A treatment cycle was a minimum of 5 days treatment. Screening was carried out at least 48 h after the treatment cycle was finished, with 24 h between each of the requested three or more samplings, which included the nasopharynx, groin, axilla, perineum and other MRSA-positive skin areas. RESULTS: Fifteen cases were retrospectively excluded (lack of outcome documentation, concomitant antibiotic therapy, open wounds). All 35 patients had colonization with MRSA before antiseptic treatment on the skin, in the groin (80%), the axilla (25.7%), the perineum (20%) or other skin areas (14.3%). Colonization at more than one skin sites was found in 34.3%. Nasal colonization was found in 21 of 28 patients (75%), 7 patients were without nasal screening prior to the antiseptic treatment. After one treatment cycle MRSA was eradicated in 25 patients (71.4%), after a second cycle the total eradication rate was 91.4%, after a third cycle the rate increased to 94.2%. No patient discontinued the antiseptic treatment due to dermal intolerance of the product. CONCLUSIONS: Progressive eradication of MRSA carriage was observed with the antiseptic soap and mupirocin. The eradication rate was not biased by concomitant antibiotic treatment, screening during treatment or lack of evidence for colonization in contrast to other studies with other preparations

Analyzing the Complex Regulatory Landscape of Hfq – an Integrative, Multi-Omics Approach

The ability of bacteria to respond to environmental change is based on the ability to coordinate, redirect and fine-tune their genetic repertoire as and when required. While we can learn a great deal from reductive analysis of individual pathways and global approaches to gene regulation, a deeper understanding of these complex signaling networks requires the simultaneous consideration of several regulatory layers at the genome scale. To highlight the power of this approach we analyzed the Hfq transcriptional/translational regulatory network in the model bacterium Pseudomonas fluorescens. We first used extensive ‘omics’ analyses to assess how hfq deletion affects mRNA abundance, mRNA translation and protein abundance. The subsequent, multi-level integration of these datasets allows us to highlight the discrete contributions by Hfq to gene regulation at different levels. The integrative approach to regulatory analysis we describe here has significant potential, for both dissecting individual signaling pathways and understanding the strategies bacteria use to cope with external challenges

Strained HgTe: a textbook 3D topological insulator

Topological insulators can be seen as band-insulators with a conducting surface. The surface carriers are Dirac particles with an energy which increases linearly with momentum. This confers extraordinary transport properties characteristic of Dirac matter, a class of materials which electronic properties are "graphene-like". We show how HgTe, a material known to exhibit 2D spin-Hall effect in thin quantum wells,\cite{Konig2007} can be turned into a textbook example of Dirac matter by opening a strain-gap by exploiting the lattice mismatch on CdTe-based substrates. The evidence for Dirac matter found in transport shows up as a divergent Hall angle at low field when the chemical potential coincides with the Dirac point and from the sign of the quantum correction to the conductivity. The material can be engineered at will and is clean (good mobility) and there is little bulk contributions to the conductivity inside the band-gap

Three-state equilibrium of Escherichia coli trigger factor

Trigger Factor (TF) is the first chaperone that interacts with nascent chains of cytosolic proteins in Escherichia coli. Although its chaperone activity requires association with ribosomes, TF is present in vivo in a 2 -3 fold molar excess over ribosomes and a fraction of it is not ribosome-associated after cell lysis. Here we show that TF follows a three-state equilibrium. Size exclusion chromatography, crosslinking and analytical ultracentrifugation revealed that uncomplexed TF dimerizes with an apparent K d of 18 µM. Dimerization is mediated by the N-terminal ribosome binding domain and the C-terminal domain of TF, whereas the central peptidyl prolyl isomerase (PPIase) and substrate binding domain does not contribute to dimerization. Crosslinking experiments showed that TF is monomeric in its ribosome-associated state. Quantitative analysis of TF binding to ribosomes revealed a dissociation constant for the TF-ribosome complex of approximately 1.2 µM. From these data we estimate that in vivo most of the ribosomes are in complex with monomeric TF. Uncomplexed TF, however, is in a monomer-dimer equilibrium with approximately two thirds of TF existing in a dimeric state

SecA cotranslationally interacts with nascent substrate proteins in vivo

SecA is an essential component of the Sec machinery in bacteria, which is responsible for transporting proteins across the cytoplasmic membrane. Recent work from our laboratory indicates that SecA binds to ribosomes. Here, we used two different approaches to demonstrate that SecA also interacts with nascent polypeptides in vivo and that these polypeptides are Sec substrates. First, we photo-cross-linked SecA to ribosomes in vivo and identified mRNAs that copurify with SecA. Microarray analysis of the copurifying mRNAs indicated a strong enrichment for proteins containing Sec-targeting sequences. Second, we used a 2-dimensional (2-D) gel approach to analyze radioactively labeled nascent polypeptides that copurify with SecA, including maltose binding protein, a well-characterized SecA substrate. The interaction of SecA with nascent chains was not strongly affected in cells lacking SecB or trigger factor, both of which also interact with nascent Sec substrates. Indeed, the ability of SecB to interact with nascent chains was disrupted in strains in which the interaction between SecA and the ribosome was defective. Analysis of the interaction of SecA with purified ribosomes containing arrested nascent chains in vitro indicates that SecA can begin to interact with a variety of nascent chains when they reach a length of ∼110 amino acids, which is considerably shorter than the length required for interaction with SecB. Our results suggest that SecA cotranslationally recognizes nascent Sec substrates and that this recognition could be required for the efficient delivery of these proteins to the membrane-embedded Sec machinery. IMPORTANCE SecA is an ATPase that provides the energy for the translocation of proteins across the cytoplasmic membrane by the Sec machinery in bacteria. The translocation of most of these proteins is uncoupled from protein synthesis and is frequently described as “posttranslational.” Here, we show that SecA interacts with nascent Sec substrates. This interaction is not dependent on SecB or trigger factor, which also interact with nascent Sec substrates. Moreover, the interaction of SecB with nascent polypeptides is dependent on the interaction of SecA with the ribosome, suggesting that interaction of the nascent chain with SecA precedes interaction with SecB. Our results suggest that SecA could recognize substrate proteins cotranslationally in order to efficiently target them for uncoupled protein translocation

Insufficient neutralization in testing a chlorhexidine-containing ethanol-based hand rub can result in a false positive efficacy assessment

BACKGROUND: Effective neutralization in testing hand hygiene preparations is considered to be a crucial element to ensure validity of the test results, especially with the difficulty to neutralize chlorhexidine gluconate. Aim of the study was to measure the effect of chemical neutralization under practical test conditions according to EN 1500. METHODS: We have investigated two ethanol-based hand rubs (product A, based on 61% ethanol and 1% chlorhexidine gluconate; product B, based on 85% ethanol). The efficacy of products (application of 3 ml for 30 s) was compared to 2-propanol 60% (v/v) (two 3 ml rubs of 30 s each) on hands artificially contaminated with Escherichia coli using a cross-over design with 15 volunteers. Pre-values were obtained by rubbing fingertips for 1 minute in liquid broth. Post-values were determined by sampling immediately after disinfection in liquid broth with and without neutralizers (0.5% lecithin, 4% polysorbate 20). RESULTS: The neutralizers were found to be effective and non-toxic. Without neutralization in the sampling fluid, the reference disinfection reduced the test bacteria by 3.7 log(10), product B by 3.3 log(10 )and product A by 4.8 log(10 )(P = 0.001; ANOVA). With neutralization the reference disinfection reduced the test bacteria by 3.5 log(10), product B by 3.3 log(10 )and product A by 2.7 log(10 )(P = 0.011; ANOVA). In comparison to the reference treatment Product B lead to a lower mean reduction than the reference disinfection but the difference was not significant (P > 0.1; Wilcoxon-Wilcox test). Without neutralizing agents in the sampling fluid, product A yielded a significantly higher reduction of test bacteria (4.8; P = 0.02) as compared to the situation with neutralizing agents (2.7; P = 0.033). CONCLUSION: The crucial step of neutralization lies in the sampling fluid itself in order to stop any residual bacteriostatic or bactericidal activity immediately after the application of the preparation, especially with chlorhexidine gluconate-containing preparations. This is particularly important at short application times such as the 30 s