The Spore Coat Protein CotE Facilitates Host Colonization by Clostridium difficile

Clostridium difficile infection (CDI) is an important hospital-acquired infection resulting from the germination of spores in the intestine as a consequence of antibiotic-mediated dysbiosis of the gut microbiota. Key to this is CotE, a protein displayed on the spore surface and carrying 2 functional elements, an N-terminal peroxiredoxin and a C-terminal chitinase domain. Using isogenic mutants, we show in vitro and ex vivo that CotE enables binding of spores to mucus by direct interaction with mucin and contributes to its degradation. In animal models of CDI, we show that when CotE is absent, both colonization and virulence were markedly reduced. We demonstrate here that the attachment of spores to the intestine is essential in the development of CDI. Spores are usually regarded as biochemically dormant, but our findings demonstrate that rather than being simply agents of transmission and dissemination, spores directly contribute to the establishment and promotion of disease

Home-based system for physical activity monitoring in patients with multiple sclerosis (Pilot study)

Background Limitations in physical activity are considered as a key problem in patients with multiple sclerosis (PwMS). Contemporary methods to assess the level of physical activity in PwMS are regular clinical observation. However, these methods either rely on high recall and accurate reporting from the patients (e.g. self-report questionnaires), or they are conducted during a particular clinical assessment with predefined activities. Therefore, the main aim of this pilot study was to develop an objective method to gather information about the real type and intensity of daily activities performed by PwMS in every-day living situations using an accelerometer. Furthermore, the accelerometer-derived measures are investigated regarding their potential for discriminating between different MS groups. Methods Eleven PwMS that were able to walk independently (EDSS&#8201;&#8804;&#8201;5) were divided into two groups: mild disability (EDSS 1&#8211;2.5; n&#8201;=&#8201;6) and moderate disability (EDSS 3 &#8211;5; n&#8201;=&#8201;5). Participants made use of an activity monitor device attached to their waist during their normal daily activities over 4 measurements. Activity parameters were assessed and compared for the time of each participant&#8217;s first measurement and follow-up measurement. Furthermore, differences between both subgroups, and the correlation of activity parameters with the clinical neurological variable (EDSS) were investigated. Results Participants showed significant decline in step count (p&#8201;=&#8201;0.008), maximum walking speed (p&#8201;=&#8201;0.02) and physical activity intensity (p&#8201;=&#8201;0.03) throughout the study period. Compared to the mild subgroup, moderate affected participant accumulated less number of steps (G1: 9214.33&#8201;±&#8201;2439.11, G2: 5018.13&#8201;±&#8201;2416.96; p&#8201;<&#8201;0.005) and were slower (G1: 1.48&#8201;±&#8201;0.19, G2: 1.12&#8201;±&#8201;0.44; p&#8201;=&#8201;0.03). Additionally, the EDSS correlated negatively with mean walking speed (r&#8201;=&#8201;- 0.71, p&#8201;=&#8201;0.01) and steps count (r&#8201;=&#8201;- 0.54, p&#8201;=&#8201;0.08). Conclusions In this study, we used a portable activity monitoring sensor to gather information about everyday physical activity in PwMS at home. We showed that objective measurements using simple 3D accelerometers can track daily physical activity fluctuation. Furthermore, they track disability changes better than clinical measures. Thus, they can help to develop activity based treatments for PwMS

Effects of Zinc Source and Level in Low ABC-4 Diets on Nursery Pig Growth Performance and Fecal Characteristics

A total of 360 weanling barrows (DNA 200 × 400; initially 13.0 ± 0.07 lb) were used in a 38-d study to evaluate the effects of diets containing different levels of a novel Zn source (HiZox, Animine Precision Minerals, Annecy, France) and different levels of crude protein (CP) in low acid-binding capacity at pH 4 (ABC-4) diets on growth performance and fecal characteristics. Pigs were randomly assigned to pens (5 pigs per pen) and pens were assigned to 1 of 6 treatments with 12 pens per treatment. Diets were fed in 3 phases: phase 1 from d 0 to 10, phase 2 from d 11 to 24, and phase 3 from d 25 to 38. All diets were formulated to have low ABC-4. Treatment 1, the negative control (NC), was formulated to contain 150 ppm of Zn (HiZox) throughout the experiment (d 0 to 38). Treatment 2, the positive control (PC), was formulated to contain 3,000 ppm (phase 1) and 2,000 ppm (phase 2) of Zn (ZnO). Treatment 3 (low HiZox) contained 500 ppm (phase 1) and 300 ppm (phase 2) of Zn. Treatment 4 (low HiZox + low CP) was formulated similar to treatment 3 but contained lower CP (19.3% CP) than the NC, PC, low, and high HiZox treatments (21.3% CP). Treatment 5 (high HiZox) contained 800 ppm (phase 1) and 500 ppm (phase 2) of Zn. Treatment 6 (high HiZox + low CP) was formulated to be similar to treatment 5 but contained less CP (19.3% CP). In phase 3, all pigs were fed a common diet containing 150 ppm of Zn (HiZox) and 21.3% CP. For the experimental period (d 0 to 24), pigs fed high HiZox + low CP had poorer F/G (P \u3c 0.05) than NC, PC, low HiZox, and high HiZox. In addition, ADG (quadratic, P = 0.007) and ADFI (quadratic, P = 0.018) increased as HiZox increased, and pigs fed diets with low CP were less feed efficient (P = 0.043) than those fed the same levels of HiZox but with high CP. Overall, pigs fed low CP diets had poorer F/G (P = 0.041) than pigs fed similar levels of HiZox with high CP. For fecal characteristics, pigs fed low CP had higher (P = 0.008) dry matter (DM) and an interaction between day and CP (P = 0.040) was detected for fecal scores with low CP diets improving stool consistency to a greater extent on d 10 than on d 23. In summary, increasing levels of HiZox improved performance of nursery pigs during phases 1 and 2, and pigs fed a regimen of 800 and 500 ppm of HiZox in the first 2 phases in low ABC-4 diets had similar performance to pigs fed pharmacological levels of Zn from ZnO in the overall period. Finally, pigs fed low CP diets had improved fecal characteristics, but poorer F/G throughout the nursery period

The High-Acceptance Dielectron Spectrometer HADES

HADES is a versatile magnetic spectrometer aimed at studying dielectron production in pion, proton and heavy-ion induced collisions. Its main features include a ring imaging gas Cherenkov detector for electron-hadron discrimination, a tracking system consisting of a set of 6 superconducting coils producing a toroidal field and drift chambers and a multiplicity and electron trigger array for additional electron-hadron discrimination and event characterization. A two-stage trigger system enhances events containing electrons. The physics program is focused on the investigation of hadron properties in nuclei and in the hot and dense hadronic matter. The detector system is characterized by an 85% azimuthal coverage over a polar angle interval from 18 to 85 degree, a single electron efficiency of 50% and a vector meson mass resolution of 2.5%. Identification of pions, kaons and protons is achieved combining time-of-flight and energy loss measurements over a large momentum range. This paper describes the main features and the performance of the detector system

Environmentally Acquired Bacillus and Their Role in C. difficile Colonization Resistance

Clostridioides difficile is an environmentally acquired, anaerobic, spore-forming bacterium which ordinarily causes disease following antibiotic-mediated dysbiosis of the intestinal microbiota. Although much is understood regarding the life cycle of C. difficile, the fate of C. difficile spores upon ingestion remains unclear, and the underlying factors that predispose an individual to colonization and subsequent development of C. difficile infection (CDI) are not fully understood. Here, we show that Bacillus, a ubiquitous and environmentally acquired, spore-forming bacterium is associated with colonization resistance to C. difficile. Using animal models, we first provide evidence that animals housed under conditions that mimic reduced environmental exposure have an increased susceptibility to CDI, correlating with a loss in Bacillus. Lipopeptide micelles (~10 nm) produced by some Bacilli isolated from the gastro-intestinal (GI)-tract and shown to have potent inhibitory activity to C. difficile have recently been reported. We show here that these micelles, that we refer to as heterogenous lipopeptide lytic micelles (HELMs), act synergistically with components present in the small intestine to augment inhibitory activity against C. difficile. Finally, we show that provision of HELM-producing Bacillus to microbiota-depleted animals suppresses C. difficile colonization thereby demonstrating the significant role played by Bacillus in colonization resistance. In the wider context, our study further demonstrates the importance of environmental microbes on susceptibility to pathogen colonization

Invariant-mass and [gamma]-ray spectroscopy using secondary, radioactive ion beams

Coulomb excitation of secondary beams (5 < Z < 20) at energies around 250 .1 MeV was explored at GSI. For low-lying states, 7-ray spectroscopy was utilized, while high-lying excitations were investigated by means of invariant-mass spectroscopy

Effect of Dietary Zinc Oxide on Morphological Characteristics, Mucin Composition and Gene Expression in the Colon of Weaned Piglets

The trace element zinc is often used in the diet of weaned piglets, as high doses have resulted in positive effects on intestinal health. However, the majority of previous studies evaluated zinc supplementations for a short period only and focused on the small intestine. The hypothesis of the present study was that low, medium and high levels of dietary zinc (57, 164 and 2,425 mg Zn/kg from zinc oxide) would affect colonic morphology and innate host defense mechanisms across 4 weeks post-weaning. Histological examinations were conducted regarding the colonic morphology and neutral, acidic, sialylated and sulphated mucins. The mRNA expression levels of mucin (MUC) 1, 2, 13, 20, toll-like receptor (TLR) 2, 4, interleukin (IL)-1β, 8, 10, interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were also measured. The colonic crypt area increased in an age-depending manner, and the greatest area was found with medium concentration of dietary zinc. With the high concentration of dietary zinc, the number of goblet cells containing mixed neutral-acidic mucins and total mucins increased. Sialomucin containing goblet cells increased age-dependently. The expression of MUC2 increased with age and reached the highest level at 47 days of age. The expression levels of TLR2 and 4 decreased with age. The mRNA expression of TLR4 and the pro-inflammatory cytokine IL-8 were down-regulated with high dietary zinc treatment, while piglets fed with medium dietary zinc had the highest expression. It is concluded that dietary zinc level had a clear impact on colonic morphology, mucin profiles and immunological traits in piglets after weaning. Those changes might support local defense mechanisms and affect colonic physiology and contribute to the reported reduction of post-weaning diarrhea

In vitro influence of dietary protein and fructooligosaccharides on metabolism of canine fecal microbiota

BACKGROUND: The present in vitro study investigated whether the utilization of fructooligosaccharides (FOS) may influence canine fecal microbial population in presence of diets differing in their protein content and digestibility. Fresh fecal samples were collected from five adult dogs, pooled, and incubated for 24 h with the undigested residue of three diets: 1, Low protein high digestibility diet (LP HD, crude protein (CP) 229 g/kg); 2, High protein high digestibility diet (HP HD, CP 304 g/kg); 3, High protein low digestibility diet (HP LD, CP 303 g/kg) that had been previously subjected to enzymatic digestion. In the in vitro fermentation study, there were six treatments: 1) LP HD; 2) HP HD 3) HP LD; 4) LP HD + FOS; 5) HP HD + FOS; 6) HP LD + FOS. Fructooligosaccharides were added at the final concentration of 1.5 g/L. Samples of fermentation fluid were collected at 6 and 24 h of incubation. RESULTS: Values of pH were reduced by FOS at 6 and 24 h (P < 0.001); conversely, low protein digestibility and high dietary protein level resulted in higher pH at both sampling times (P < 0.001). At 24 h, FOS lowered ammonia (−10 %; P < 0.001) and resulted (P < 0.05) in higher concentrations of total volatile fatty acids (VFA) (+43 %), acetic acid (+14 %), propionic acid (+75 %) and n-butyric acid (+372 %). Conversely, at 24 h, low protein digestibility resulted (P < 0.01) in lower concentrations of acetic acid (−26 %), propionic acid (−37 %) and total VFA (−21 %). Putrescine concentrations were increased at 6 and 24 h of fermentation by low protein digestibility (+21 and 22 %, respectively; P < 0.05) and FOS (+18 and 24 %, respectively; P < 0.01). After 24 h of fermentation, high dietary protein level resulted in lower counts of lactobacilli and enterococci (−0.5 and −0.7 log cells/mL, respectively; P < 0.05) whereas low protein digestibility tended to increase counts of C. perfringens (+0.2 log cells/mL; P = 0.07). CONCLUSIONS: Results from the present study showed that diets rich in protein may exert negative influences on the canine intestinal ecosystem, slightly increasing the presence of ammonia and reducing counts of lactobacilli and enterococci. Moreover, the presence of poorly digestible protein resulted in lower concentrations of VFA. Conversely, administration of FOS may improve metabolism of canine intestinal microbiota, reducing ammonia concentrations and enhancing VFA production