Comparative genomic analysis reveals significant enrichment of mobile genetic elements and genes encoding surface structure-proteins in hospital-associated clonal complex 2 Enterococcus faecalis

Background  

Enterococci rank among the leading causes of nosocomial infections. The failure to identify pathogen-specific genes in Enterococcus faecalis has led to a hypothesis where the virulence of different strains may be linked to strain-specific genes, and where the combined endeavor of the different gene-sets result in the ability to cause infection. Population structure studies by multilocus sequence typing have defined distinct clonal complexes (CC) of E. faecalis enriched in hospitalized patients (CC2, CC9, CC28 and CC40).     

Regenerative potential of human muscle stem cells in chronic inflammation

Introduction

Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle.

Methods

As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation.

Results

After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group.

Conclusions

In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate.     

NrdH-redoxin protein mediates high enzyme activity in manganese-reconstituted ribonucleotide reductase from Bacillus anthracis

Bacillus anthracis is a severe mammalian pathogen encoding a class Ib ribonucleotide reductase (RNR). RNR is a universal enzyme that provides the four essential deoxyribonucleotides needed for DNA replication and repair. Almost all Bacillus spp. encode both class Ib and class III RNR operons, but the B. anthracis class III operon was reported to encode a pseudogene, and conceivably class Ib RNR is necessary for spore germination and proliferation of B. anthracis upon infection. The class Ib RNR operon in B. anthracis encodes genes for the catalytic NrdE protein, the tyrosyl radical metalloprotein NrdF, and the flavodoxin protein NrdI. The tyrosyl radical in NrdF is stabilized by an adjacent Mn(2)(III) site (Mn-NrdF) formed by the action of the NrdI protein or by a Fe(2)(III) site (Fe-NrdF) formed spontaneously from Fe(2+) and O(2). In this study, we show that the properties of B. anthracis Mn-NrdF and Fe-NrdF are in general similar for interaction with NrdE and NrdI. Intriguingly, the enzyme activity of Mn-NrdF was approximately an order of magnitude higher than that of Fe-NrdF in the presence of the class Ib-specific physiological reductant NrdH, strongly suggesting that the Mn-NrdF form is important in the life cycle of B. anthracis. Whether the Fe-NrdF form only exists in vitro or whether the NrdF protein in B. anthracis is a true cambialistic enzyme that can work with either manganese or iron remains to be established.     

The risk for depression in patients with ankylosing spondylitis: a population-based cohort study

Introduction

Depression is frequent in ankylosing spondylitis (AS) patients. However, epidemiological data about the potential increase in risk are lacking. This study compares the rate of doctor-diagnosed depression in a well defined cohort of AS patients to the general population seeking care.

Methods

The Skåne Healthcare Register comprises healthcare data of each resident in Region Skåne, Sweden (population 1.2 million), including ICD-10 diagnoses. Using physician coded consultation data from years 1999 to 2011, we calculated depression consultation rates for all AS patients. We obtained standardized depression-rate ratios by dividing the observed depression rate in AS patients by the expected rate based on the corresponding age- and sex-specific rates of depression in the general population seeking care. A ratio >1 equals a higher rate of depression among AS patients.

Results

The AS cohort consisted of 1738 subjects (65% men) with a mean age of 54 years. The reference population consisted of 967,012 subjects. During the 13-year observation period 10% (n = 172) of the AS cohort had a doctor-diagnosed depression compared to 6% (n = 105) to be expected. The standardized estimate of depression-rate ratio was 1.81 (95% confidence interval 1.44 to 2.24) in women men and 1.49 (1.20 to 1.89) in men.

Conclusions

The rate of doctor-diagnosed depression is increased about 80% in female and 50% in male AS patients. Future challenges are to timely identify and treat the AS patients who suffer from depression.     

Association between environmental and climatic risk factors and the spatial distribution of cystic and alveolar echinococcosis in Kyrgyzstan

BackgroundCystic and alveolar echinococcosis (CE and AE) are neglected tropical diseases caused by Echinococcus granulosus sensu lato and E. multilocularis, and are emerging zoonoses in Kyrgyzstan. In this country, the spatial distribution of CE and AE surgical incidence in 2014-2016 showed marked heterogeneity across communities, suggesting the presence of ecological determinants underlying CE and AE distributions.Methodology/Principal findingsFor this reason, in this study we assessed potential associations between community-level confirmed primary CE (no.=2359) or AE (no.=546) cases in 2014-2016 in Kyrgyzstan and environmental and climatic variables derived from satellite-remote sensing datasets using conditional autoregressive models. We also mapped CE and AE relative risk. The number of AE cases was negatively associated with 10-year lag mean annual temperature. Although this time lag should not be considered as an exact measurement but with associated uncertainty, it is consistent with the estimated 10–15-year latency following AE infection. No associations were detected for CE. We also identified several communities at risk for CE or AE where no disease cases were reported in the study period.Conclusions/SignificanceOur findings support the hypothesis that CE is linked to an anthropogenic cycle and is less affected by environmental risk factors compared to AE, which is believed to result from spillover from a wild life cycle. As CE was not affected by factors we investigated, hence control should not have a geographical focus. In contrast, AE risk areas identified in this study without reported AE cases should be targeted for active disease surveillance in humans. This active surveillance would confirm or exclude AE transmission which might not be reported with the present passive surveillance system. These areas should also be targeted for ecological investigations in the animal hosts.     

A novel liver specific isoform of the rat LAR transcript is expressed as a truncated isoform encoded from a 5'UTR located within intron 11

Background  

The leukocyte common antigen related receptor (LAR) protein has been shown to modulate the signal transduction of a number of different growth factors, including insulin and insulin-like growth factor 1. Splice variants exhibit differing roles and are expressed according to tissue type and developmental stage.     

Enterococcal surface protein Esp is not essential for cell adhesion and intestinal colonization of Enterococcus faecium in mice

Background  

Enterococcus faecium has globally emerged as a cause of hospital-acquired infections with high colonization rates in hospitalized patients. The enterococcal surface protein Esp, identified as a potential virulence factor, is specifically linked to nosocomial clonal lineages that are genetically distinct from indigenous E. faecium strains. To investigate whether Esp facilitates bacterial adherence and intestinal colonization of E. faecium, we used human colorectal adenocarcinoma cells (Caco-2 cells) and an experimental colonization model in mice.