An RND-Type Efflux System in Borrelia burgdorferi Is Involved in Virulence and Resistance to Antimicrobial Compounds

Borrelia burgdorferi is remarkable for its ability to thrive in widely different environments due to its ability to infect various organisms. In comparison to enteric Gram-negative bacteria, these spirochetes have only a few transmembrane proteins some of which are thought to play a role in solute and nutrient uptake and excretion of toxic substances. Here, we have identified an outer membrane protein, BesC, which is part of a putative export system comprising the components BesA, BesB and BesC. We show that BesC, a TolC homolog, forms channels in planar lipid bilayers and is involved in antibiotic resistance. A besC knockout was unable to establish infection in mice, signifying the importance of this outer membrane channel in the mammalian host. The biophysical properties of BesC could be explained by a model based on the channel-tunnel structure. We have also generated a structural model of the efflux apparatus showing the putative spatial orientation of BesC with respect to the AcrAB homologs BesAB. We believe that our findings will be helpful in unraveling the pathogenic mechanisms of borreliae as well as in developing novel therapeutic agents aiming to block the function of this secretion apparatus

Evidence of Inbreeding Depression on Human Height

WOS:000306840400001Peer reviewe

Analysis of Vibration Measurements on Moving Trains

The development in society means that infrastructure like ballasted railway systems is facing challenges due to requests for a increased number of high-speed trains and heavier freight trains. This implies that ballasted railways get an increased impact from larger dynamic loads. The question is how the ballasted railways are today affected by dynamic loading and how will an increase in train speed and weight change the soil behavior within the railway embankment. A method of investigating soil behavior is via geophysical measurements. Accelerometers are commonly used for vibration measurements and by installing them on trains, measurements are possible to perform for complete railway sections. The knowledge of Eigen frequencies for various track components and soil layers are essential when considering frequency analysis of accelerometer measurements. Specifically, this means that the analysis is about detecting resonance of different components. From the actual case study, a good correlation is obtained between the expected Eigen frequencies and the measurement results. Thus, an assessment of the dynamic loadings influences on various soil layers and ballast has been possible to perform. Resonance of a soil layer means that the particles will be rearranged and degraded. For the case when saturated soil layers are subjected to resonance a phenomenon called liquefaction can occur if the pore pressures increases to the level were soil layers lose their effective stresses. Therefore, the most critical finding in this study is liquefaction because it leads to a loss in bearing capacity followed by settlements. Old railway tracks where little or no information exists of the soil conditions are the most suitable areas were this measurement and analysis method is of special use. Consequently, conventional borehole sampling can be reduced.ISBN för värdpublikation: 978-981-15-0449-5, 978-981-15-0450-1</p

Body mass index in middle life and future risk of hospital admission for psychoses or depression: findings from the Renfrew/Paisley study

Background. There is evidence that greater body mass index (BMI) protects against depression, schizophrenia and suicide. However, there is a need for prospective studies. Method. We examined the association of BMI with future hospital admissions for psychoses or depression/anxiety disorders in a large prospective study of 7036 men and 8327 women. Weight and height were measured at baseline (1972-76) when participants were aged 45-64. Follow-up was for a median of 29 years. Results. Greater BMI and obesity were associated with a reduced risk of hospital admission for psychoses and depression/anxiety in both genders, with the magnitude of these associations being the same for males and females. With adjustment for age, sex, smoking and social class, a I standard deviation (S.D.) greater BMI at baseline was associated with a rate ratio of 0.91 [95 % confidence interval (CI) 0.82-1.01] for psychoses and 0.87 (95 % CI 0.77-0.98) for depression/anxiety. Further adjustment for baseline psychological distress and total cholesterol did not alter these associations. Conclusions. Our findings add to the growing body of evidence that suggests that greater BMI is associated with a reduced risk of major psychiatric outcomes. Long-term follow-up of participants in randomized controlled trials of interventions that effectively result in weight loss and the use of genetic variants that are functionally related to obesity as instrumental variables could help to elucidate whether these associations are causal

Direct repeat-mediated deletion of a type IV pilin gene results in major virulence attenuation of Francisella tularensis.

Francisella tularensis, the causative agent of tularaemia, is a highly infectious and virulent intracellular pathogen. There are two main human pathogenic subspecies, Francisella tularensis ssp. tularensis (type A), and Francisella tularensis ssp. holarctica (type B). So far, knowledge regarding key virulence determinants is limited but it is clear that intracellular survival and multiplication is one major virulence strategy of Francisella. In addition, genome sequencing has revealed the presence of genes encoding type IV pili (Tfp). One genomic region encoding three proteins with signatures typical for type IV pilins contained two 120 bp direct repeats. Here we establish that repeat-mediated loss of one of the putative pilin genes in a type B strain results in severe virulence attenuation in mice infected by subcutaneous route. Complementation of the mutant by introduction of the pilin gene in cis resulted in complete restoration of virulence. The level of attenuation was similar to that of the live vaccine strain and this strain was also found to lack the pilin gene as result of a similar deletion event mediated by the direct repeats. Presence of the pilin had no major effect on the ability to interact, survive and multiply inside macrophage-like cell lines. Importantly, the pilin-negative strain was impaired in its ability to spread from the initial site of infection to the spleen. Our findings indicate that this putative pilin is critical for Francisella infections that occur via peripheral routes