Fatigue, anxiety, depression and quality of life in kidney transplant recipients, haemodialysis patients, patients with a haematological malignancy and healthy controls.

BACKGROUND: The impact of haemodialysis (HD) and kidney transplantation on quality of life (QoL) is often underestimated due to a lack of comparative studies with other patient groups. METHODS: We conducted a cross-sectional cohort study in 168 patients including HD patients, kidney transplant recipients (KTR), patients with a haematological malignancy either receiving chemotherapy or in remission and healthy controls. All participants completed the 36-item short form survey of health-related quality of life, the Checklist Individual Strength and the Hospital Anxiety and Depression Scale questionnaire. RESULTS: HD patients and haematological patients undergoing chemotherapy were more frequently severely fatigued (53.3% and 50% of cases) compared with KTR (33.3%), haematological patients in remission (23.3%) and healthy controls (12.1%, P < 0.001). There were no significant differences in anxiety rates. HD patients and haematological patients undergoing chemotherapy were most likely to be depressed (33.3% and 25%), compared with 16.7% of KTR, 20% of haematological patients in remission and 8.6% of healthy controls (P = 0.066). KTR reported the largest positive health change (+27%, P < 0.001), but still had a lower overall QoL than healthy controls, comparable to haematological patients in remission. HD and chemotherapy patients reported the lowest QoL scores. CONCLUSIONS: Fatigue and depression are common in HD patients, resulting in a low QoL, comparable to haematological patients receiving chemotherapy. KTR do better, with scores similar to patients with a haematological malignancy in remission, but still have a lower QoL than healthy controls.

Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide.

BACKGROUND: Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP receptors in glial activation in response to an inflammatory challenge induced by LPS. METHODS: Cultures of mouse microglia or astroglia cells were treated with LPS in the presence or absence of COX-2 inhibitors, and the production of PGE2 was measured by ELISA. Cells were treated with PGE2, and the effect on LPS-induced expression of TNF-α messenger RNA (mRNA) and protein was studied in the presence or absence of drug antagonists of the four EP receptors. EP receptor expression and the effects of EP2 and EP4 agonists and antagonists were studied at different time points after LPS. RESULTS: PGE2 production after LPS was COX-2-dependent. PGE2 reduced the glial production of TNF-α after LPS. Microglia expressed higher levels of EP4 and EP2 mRNA than astroglia. Activation of EP4 or EP2 receptors with selective drug agonists attenuated LPS-induced TNF-α in microglia. However, only antagonizing EP4 prevented the PGE2 effect demonstrating that EP4 was the main target of PGE2 in naïve microglia. Moreover, the relative expression of EP receptors changed during the course of classical microglial activation since EP4 expression was strongly depressed while EP2 increased 24 h after LPS and was detected in nuclear/peri-nuclear locations. EP2 regulated the expression of iNOS, NADPH oxidase-2, and vascular endothelial growth factor. NADPH oxidase-2 and iNOS activities require the oxidation of NADPH, and the pentose phosphate pathway is a main source of NADPH. LPS increased the mRNA expression of the rate-limiting enzyme of the pentose pathway glucose-6-phosphate dehydrogenase, and EP2 activity was involved in this effect. CONCLUSIONS: These results show that while selective activation of EP4 or EP2 exerts anti-inflammatory actions, EP4 is the main target of PGE2 in naïve microglia. The level of EP receptor expression changes from naïve to primed microglia where the COX-2/PGE2/EP2 axis modulates important adaptive metabolic changes.

Ruminococcus gnavus E1 modulates mucin expression and intestinal glycosylation.

AIMS: The molecular cross-talk between commensal bacteria and the gut play an important role in the maintenance of the intestinal homeostasis and general health. Here, we studied the impact of a major Gram-positive anaerobic bacterium of the human gut microbiota, that is, Ruminococcus gnavus on the glycosylation pattern and the production of intestinal mucus by the goblet cells. METHODS AND RESULTS: Our results showed that R. gnavus E1 specifically increases the expression and the glycosylation level of the intestinal glyco-conjugates by goblet cells in the colonic mucosa of mono-associated mice with R. gnavus E1 as well as in human HT29-MTX cells. Such an effect was mediated through induction of the level of mRNA encoding for the major intestinal gel-forming mucin such as MUC2 and various glycosyltransferase enzymes. CONCLUSIONS: This study demonstrates for the first time that R. gnavus E1 possess the ability to modulate the glycosylation profile of the glyco-conjugate molecules and mucus in goblet cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Furthermore, we demonstrated that R. gnavus E1 modified specifically the glycosylation pattern and MUC2 expression by means of a small soluble factor of peptidic nature (<3 kDa) and heat stable in the HT29-MTX cell.

Arginine transport is impaired in C57Bl/6 mouse macrophages as a result of a deletion in the promoter of Slc7a2 (CAT2), and susceptibility to Leishmania infection is reduced.

Host genetic factors play a crucial role in immune response. To determine whether the differences between C57Bl/6 and BALB-C mice are due only to the production of cytokines by T-helper 1 cells or T-helper 2 cells, we obtained bone marrow-derived macrophages from both strains and incubated them with these cytokines. Although the induction of Nos2 and Arg1 was similar in the 2 strains, infectivity to Leishmania major differed, as did macrophage uptake of arginine, which was higher in BALB-C macrophages. The levels of interferon γ- and interleukin 4-dependent induction of the cationic amino acid transporter SLC7A2 (also known as "cationic amino acid transporter 2," or "CAT2") were decreased in macrophages from C57Bl/6 mice. This reduction was a result of a deletion in the promoter of one of the 4 AGGG repeats. These results demonstrate that the availability of arginine controls critical aspects of macrophage activation and reveal a factor for susceptibility to Leishmania infection.

Induction of COX-2 enzyme and down-regulation of COX-1 expression by lipopolysaccharide (LPS) control prostaglandin E2 production in astrocytes.

Pathological conditions and pro-inflammatory stimuli in the brain induce cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism mediating the production of prostanoids that, among other actions, have strong vasoactive properties. Although low basal cerebral COX-2 expression has been reported, COX-2 is strongly induced by pro-inflammatory challenges, whereas COX-1 is constitutively expressed. However, the contribution of these enzymes in prostanoid formation varies depending on the stimuli and cell type. Astrocyte feet surround cerebral microvessels and release molecules that can trigger vascular responses. Here, we investigate the regulation of COX-2 induction and its role in prostanoid generation after a pro-inflammatory challenge with the bacterial lipopolysaccharide (LPS) in astroglia. Intracerebral administration of LPS in rodents induced strong COX-2 expression mainly in astroglia and microglia, whereas COX-1 expression was predominant in microglia and did not increase. In cultured astrocytes, LPS strongly induced COX-2 and microsomal prostaglandin-E(2) (PGE(2)) synthase-1, mediated by the MyD88-dependent NFκB pathway and influenced by mitogen-activated protein kinase pathways. Studies in COX-deficient cells and using COX inhibitors demonstrated that COX-2 mediated the high production of PGE(2) and, to a lesser extent, other prostanoids after LPS. In contrast, LPS down-regulated COX-1 in an MyD88-dependent fashion, and COX-1 deficiency increased PGE(2) production after LPS. The results show that astrocytes respond to LPS by a COX-2-dependent production of prostanoids, mainly vasoactive PGE(2), and suggest that the coordinated down-regulation of COX-1 facilitates PGE(2) production after TLR-4 activation. These effects might induce cerebral blood flow responses to brain inflammation.

Functional analysis of family GH36 α-galactosidases from Ruminococcus gnavus E1: insights into the metabolism of a plant oligosaccharide by a human gut symbiont.

Ruminococcus gnavus belongs to the 57 most common species present in 90% of individuals. Previously, we identified an α-galactosidase (Aga1) belonging to glycoside hydrolase (GH) family 36 from R. gnavus E1 (M. Aguilera, H. Rakotoarivonina, A. Brutus, T. Giardina, G. Simon, and M. Fons, Res. Microbiol. 163:14-21, 2012). Here, we identified a novel GH36-encoding gene from the same strain and termed it aga2. Although aga1 showed a very simple genetic organization, aga2 is part of an operon of unique structure, including genes putatively encoding a regulator, a GH13, two phosphotransferase system (PTS) sequences, and a GH32, probably involved in extracellular and intracellular sucrose assimilation. The 727-amino-acid (aa) deduced Aga2 protein shares approximately 45% identity with Aga1. Both Aga1 and Aga2 expressed in Escherichia coli showed strict specificity for α-linked galactose. Both enzymes were active on natural substrates such as melibiose, raffinose, and stachyose. Aga1 and Aga2 occurred as homotetramers in solution, as shown by analytical ultracentrifugation. Modeling of Aga1 and Aga2 identified key amino acids which may be involved in substrate specificity and stabilization of the α-linked galactoside substrates within the active site. Furthermore, Aga1 and Aga2 were both able to perform transglycosylation reactions with α-(1,6) regioselectivity, leading to the formation of product structures up to [Hex](12) and [Hex](8), respectively. We suggest that Aga1 and Aga2 play essential roles in the metabolism of dietary oligosaccharides and could be used for the design of galacto-oligosaccharide (GOS) prebiotics, known to selectively modulate the beneficial gut microbiota.

Matrix metalloproteinase-9 and cell division in neuroblastoma cells and bone marrow macrophages.

Matrix metalloproteinases (MMPs) degrade the extracellular matrix and carry out key functions in cell development, cancer, injury, and regeneration. In addition to its well recognized extracellular action, functional intracellular MMP activity under certain conditions is supported by increasing evidence. In this study, we observed higher gelatinase activity by in situ zymography and increased MMP-9 immunoreactivity in human neuroblastoma cells and in bone marrow macrophages undergoing mitosis compared with resting cells. We studied the pattern of immunoreactivity at the different stages of cell division by confocal microscopy. Immunostaining with different monoclonal antibodies against MMP-9 revealed a precise, dynamic, and well orchestrated localization of MMP-9 at the different stages of cell division. The cellular distribution of MMP-9 staining was studied in relation to that of microtubules. The spatial pattern of MMP-9 immunoreactivity suggested some participation in both the reorganization of the nuclear content and the process of chromatid segmentation. We then used several MMP-9 inhibitors to find out whether MMP-9 might be involved in the cell cycle. These drugs impaired the entry of cells into mitosis, as revealed by flow cytometry, and reduced cell culture growth. In addition, the silencing of MMP-9 expression with small interfering RNA also reduced cell growth. Taken together, these results suggest that intracellular MMP-9 is involved in the process of cell division in neuroblastoma cells and in primary cultures of macrophages.

Reduction of smoking in Dutch adolescents over the past decade and its health gains: a repeated cross-sectional study.

BACKGROUND: Smoking is the main preventable lifestyle-related risk factor threatening human health. In this study, time trends in smoking behaviour between 1996 and 2005 among adolescents enrolled in secondary school were assessed. METHODS: In 1996, 2001 and 2005, a survey was conducted in the south-eastern region of the Netherlands. All students in second and fourth year of secondary education (1996: n = 20 000; 2001: n = 27 500; 2005: n = 24 000) were asked to complete a questionnaire about their smoking behaviour. A simulation model was used to estimate lifetime health gains related to the observed trends. RESULTS: In 1996, 2001 and 2005, the number of questionnaires analysed were 13 554 (68%), 20 767 (76%) and 17 896 (75%), respectively. The results show a decrease in 'ever smoking' as well as 'current smoking' between 1996 and 2005. Among second year high school students, current smoking prevalence decreased from 22.2% in 1996 to 8.0% in 2005 (P(trend) < 0.001). Among fourth year students, current smoking declined from 37.5% in 1996 to 22.0% in 2005 (P(trend) < 0.001). Time trends were not influenced by gender or educational level. Model projections show that if these students not take up smoking later in life, 11 500 new cases of COPD, 3400 new cases of lung cancer and 1800 new cases of myocardial infarction could be prevented for the Dutch 13-year-olds. CONCLUSION: This study found that, in the past decade, smoking prevalence among adolescents has declined by almost 50%, potentially resulting in a considerable reduction in new cases of COPD or lung cancer.

Production of an antibacterial substance in the digestive tract involved in colonization-resistance against Clostridium perfringens.

Ruminococcus gnavus E1, Bacteroides thetaiotaomicron LEMF4, Clostridium hathewayi LEMC7, and Clostridium orbiscindens LEMH9 were isolated from ex germ-free mice inoculated with a human faecal microbiota. When initially germ-free mice who were previously inoculated with the strain E1 alone, or a four-strain consortium [E1, LEMF4, LEMC7, and LEMH9], were then challenged with 108 counts of Clostridium perfringens; the target strain was rapidly eliminated from the digestive tract of the animals (<10² cfu g⁻¹ of faeces). R. gnavus E1 was able to produce a diffusible anti-C. perfringens substance that accumulated in the faeces of monoassociated animals, but failed to be detected in the faeces of mice associated with the four-strain consortium. The capability to produce the antibacterial substance was transferred in the digestive tract of gnotobiotic mice to a Dorea longicatena strain. Further experiments realized with the D. longicatena wild type strain and the transconjugant support the assumption that the diffusible antibacterial substance was necessary for obtaining the antagonistic effect against C. perfringens, but that it acted as a precursor in the mechanism of interaction of the four-strain consortia.

Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut.

We have shown that bacterial mutation rates change during the experimental colonization of the mouse gut. A high mutation rate was initially beneficial because it allowed faster adaptation, but this benefit disappeared once adaptation was achieved. Mutator bacteria accumulated mutations that, although neutral in the mouse gut, are often deleterious in secondary environments. Consistently, the competitiveness of mutator bacteria is reduced during transmission to and re-colonization of similar hosts. The short-term advantages and long-term disadvantages of mutator bacteria could account for their frequency in nature.

Receptor-initiated activation of cells and their oncogenes by herpes-family viruses.

The interaction of human cytomegalovirus (HCMV) with the cell membrane has been shown to initiate a cascade of physiologic and biochemical responses that result in the transcriptional activation of specific cellular proto-oncogenes. The cell-activation responses initiated by the virus membrane interaction appear to be important for efficient HCMV replication, as pharmacologic inhibition of cell activation responses significantly reduces the expression of immediate early viral genes and the production of infectious progeny virus. Cellular receptor proteins for other viruses have been shown to be molecules with physiologic activities. Binding of virus to these receptors may trigger the cell to initiate changes that are important for efficient viral replication. These viruses may also trigger inappropriate physiologic responses in the absence of viral replication, thereby causing more covert manifestations of viral pathology.

Cytomegalovirus-enhanced induction of chromosome aberrations in human peripheral blood lymphocytes treated with potent genotoxic agents.

Human cytomegalovirus (HCMV) has been shown to increase the frequency of chromosome aberrations, primarily chromatid-type, in human peripheral blood lymphocytes (PBLs). Because HCMV persists in most humans, pathologically activates cells, and may perturb the cell cycle, we investigated the possibility that HCMV-infected cells have a modified sensitivity to chromosome damage induced by genotoxic chemicals. Uninfected PBLs exposed to bleomycin (3 to 100 micrograms/ml) demonstrated a linear increase in the frequency of chromosome aberrations. HCMV infection of PBLs at an intensity that did not cause detectable damage followed by exposure to the same concentrations of bleomycin resulted in a significant enhancement (p less than 0.01) in the frequency of chromosome aberrations relative to the effect of bleomycin alone. A more than additive enhancement of the frequency of chromosome aberrations was also noted in HCMV-infected PBLs exposed to 4-hydroxyaminoquinoline-1-oxide (4-HAQO; 0.1 to 0.3 micrograms/ml) relative to uninfected cells treated with 4-HAQO alone. No increase in the percentage of aberrant cells or the frequency of chromosome aberrations was observed in HCMV-infected cells treated with 4-nitroquinoline-1-oxide (4-NQO) relative to similarly treated uninfected PBLs. These results suggest that HCMV can potentiate the induction of chromosome aberrations in human PBLs caused by potent DNA damaging agents.

The intellectual property landscape in the field of plasmid-based gene therapy.

As plasmid-based gene therapy products progress through clinical trials commercial entities begin to focus on the intellectual property associated with the methods and specific compositions used in these therapies. As the number of patents covering gene therapy components and methods increases it becomes increasingly difficult for a single entity to collect all of the necessary rights to be able to offer gene therapy products to consumers. The present report briefly describes the relevance of patents to product commercialization and describes certain key patents that may affect the ultimate commercialization potential of this new and exciting technology.

Multiple herpesviruses in saliva of HIV-infected individuals.

Oral infections with human herpesviruses cause increased morbidity in patients infected with HIV. In this study, multiple HHVs were often isolated from the saliva of HIV-seropositive dental patients, but their isolation rate did not differ substantially from rates reported for the general population, except for human cytomegalovirus.

Outcome for the first 85 patients treated with the functional endoscopic sinus surgery technique.

Out of 85 patients operated on with the functional endoscopic sinus surgery (FESS) technique, 62 patients (73%), representing 105 operated sides, participated in an endoscopic follow-up with concomitant questionnaire concerning symptoms and patient's evaluation of the result. On 61 operative sides were performed polypectomies, 43 sides were operated on because of chronic recurrent sinusitis. Twelve patients (corresponding to 17 sides) were re-operated on. The mean follow-up period was 16 months for the patients with one operation, for those with re-operation it was 10 months. Eighty-two per cent of the patients reported subjectively marked or full improvement, 18% had experienced no change or slight improvement. By endoscopy, 43 operated sides (41.0%) were considered fully normal at follow-up. Residual polyposis was seen in 21 of 61 operated sides (35.9%) with pre-operative polyposis, and purulent discharge was seen in 11 sides (10.5% of all operated sides). The discrepancy between subjective satisfaction and objectively-assessed recurrent or residual pathology indicates a need for further elucidation of the aetiologies for chronic inflammatory sinonasal diseases. Obstruction of the drainage pathways around the ostiomeatal complex cannot explain all cases of sinusitis and is hardly aetiological in polyposis. Nevertheless, FESS is presently an adequate treatment in obtaining immediate relief in most cases of medically resistant sinusitis and polyposis.

[Quality of post-operative pain therapy after subacromial decompression of the shoulder with resection of the lateral clavicula by arthroscopy]. / Qualität der postoperativen Schmerztherapie nach arthroskopischer subakromialer Schulterdekompression mit Resektion der lateralen Klavikula.

BACKGROUND: Shoulder impingement is one of the most common orthopaedic arthropathies. A minimally invasive surgery is indicated in cases of persistent symptoms or non-responders to conservative pain therapy. Normally, strong postoperative pain of the shoulder requires an effective pain therapy. PATIENTS/MATERIAL AND METHODS: 100 patients suffering from shoulder impingement with involvement of the acromioclavicular joint (55 male, 45 female, mean age 56, age range 37-78 years) were operated in 2007 and 2008 in the department of orthopaedics of the LVR-hospital. We aimed to evaluate the value of a subacromial pain catheter with ropivacaine (n = 33) compared to a conservative pain therapy ("Würzburger Schmerztropf"/tramadol, novaminsulfon and metroclopramid and "Hettinger Infusion"/tramadol, novaminsulfon, dimenhydrinate as needed) alone (n = 34) or with an additional intraoperative administration of a single dose of ropivacaine (n = 33) after arthroscopic subacromial decompression of the shoulder with resection of the lateral clavicula. Additionally, patients of all three groups received a baseline analgesia with cryotherapy and diclofenac. RESULTS: Patients who received pain therapy by subacromial catheter reported less pain in the first 48 hours after surgery compared to ropivacaine intraoperatively and a standard pain therapy. Although all three methods achieved a significant pain reduction in the postoperative period, patients with subacromial catheter claimed the highest satisfaction with the therapy. Moreover, we could show that the subacromial pain catheter is a very efficient method with a high acceptance by the patients which is easy to perform and free of complications when considering the respective hygienic measures.

"Can a tu lado": una intervención canina en adolescentes hospitalizados con patología psiquiátrica / "A dog beside to you": a dog assisted intervention for hospitalized adolescents with psychiatric illness

Introducción. Los adolescentes con patología psiquiátrica aguda pueden precisar hospitalizaciones repetidas y prolongadas. La intervención con perro de asistencia (IPA) durante el ingreso puede contribuir al proceso de recuperación. Pacientes y método. Veintisiete sujetos (9 varones) de entre 13 y 18 años ingresados consecutivamente en la Unidad de Psiquiatría de Adolescentes participaron semanalmente, por asignación aleatoria, en una IPA grupal de 45 minutos de duración durante su ingreso. Se comparó el efecto a corto plazo de la IPA sobre la ansiedad estado (escala de Spielberger) y la evaluación subjetiva tras cada IPA respecto al registrado las semanas sin encuentro. El grado de afectación clínica se valoró al ingreso y al alta mediante la escala de Impresión Clínica Global (CGI). Resultados. Los adolescentes presentaban gravedad clínica moderada al ingreso (mediana CGI: 5). La mediana del tiempo de ingreso fue de 24 días. Se realizaron valoraciones semanales durante 5 meses ininterrumpidamente (11 semanas con intervención canina y 10 sin ella). De las 78 evaluaciones individuales, 5 fueron descartadas por estar incompletas, y se analizaron 73 (39 con intervención y 34 sin ella). La ansiedad estado se redujo después de la intervención (-0,54 DE; p=0,004), pero no lo hizo en el grupo control. Los adolescentes consideraron la intervención útil e integradora. Conclusiones. Los adolescentes con patología psiquiátrica aguda que precisan hospitalización, presentan una afectación moderadamente grave. La intervención canina grupal es factible, reduce la ansiedad y es considerada por los ingresados útil, especialmente en la mejora de la relación con los otros adolescentes, aunque no es capaz de normalizar la percepción de la hospitalización (AU)

Background. The adolescents with acute psychiatric disorders may need prolonged and repeated hospitalizations. Dog assisted interventions during their stay may accelerate their recovery. Patients and method. Twenty seven adolescents (9 male), aged between 13 and 18 years old who were consecutively admitted in the Psychiatric Adolescent Unit, were randomly assigned every week to participate in a dog assisted group intervention with the other mates of the Unit for 45 minutes along their hospitalization. The immediate effect of the intervention was assessed with the Spielberger Anxiety State Scale (STAI) and subjective responses to qualitative questions completed by the adolescents both the weeks with intervention and without it. Clinical severity was assessed at admission and at discharge with the Clinical Global Impressions (CGI) scale. Results. Median CGI score at admission was 5 (“markedly ill”). Median stay was 24 days. Weekly assessments were done during the 5 month study period (11 weeks with dog assisted intervention and 10 without it). Seventy three individual assessments out of 78 (5 were incomplete and accordingly discarded) were analysed. The anxiety state score was reduced in the intervention group (-0,54 SD; p=0,004) but not in the control group. The adolescents considered the intervention useful, especially to improve relationships. Conclusions. The adolescents with acute psychiatric disorders requiring hospitalization are markedly ill. Dog assisted group intervention is feasible in this context. This activity reduces patients anxiety and the inmates consider it useful, especially to easen their relationship, although it fails to normalize their hospital perception (AU)

Ruminococcin C, a new anti-Clostridium perfringens bacteriocin produced in the gut by the commensal bacterium Ruminococcus gnavus E1.

When colonizing the digestive tract of mono-associated rats, Ruminococcus gnavus E1 - a bacterium isolated from human faeces - produced a trypsin-dependent anti-Clostridium perfringens substance collectively named Ruminococcin C (RumC). RumC was isolated from the caecal contents of E1-monocontaminated rats and found to consist of two antimicrobial fractions: a single peptide (RumCsp) of 4235 Da, and a mixture of two other peptides (RumCdp) with distinct molecular masses of 4324 Da and 4456 Da. Both RumCsp and RumCdp were as effective as metronidazole in combating C. perfringens and their activity spectra against different pathogens were established. Even if devoid of synergistic activity, the combination of RumCsp and RumCdp was observed to be much more resistant to acidic pH and high temperature than each fraction tested individually. N-terminal sequence analysis showed that the primary structures of these three peptides shared a high degree of homology, but were clearly distinct from previously reported amino acid sequences. Amino acid composition of the three RumC peptides did not highlight the presence of any Lanthionine residue. However, Edman degradation could not run beyond the 11th amino acid residue. Five genes encoding putative pre-RumC-like peptides were identified in the genome of strain E1, confirming that RumC was a bacteriocin. This is the first time that a bacteriocin produced in vivo by a human commensal bacterium was purified and characterized.