A fusion protein derived from Moraxella catarrhalis and Neisseria meningitidis aimed for immune modulation of human B cells.

Moraxella IgD-binding protein (MID) is a well characterized trimeric autotransporter that specifically targets the IgD of B cells. We fused the membrane anchor of the meningococcal autotransporter NhhA with the IgD-binding region of MID (aa 962-1200) to create a chimeric protein designated as NID. The aim was to use this specific targeting to provide a better vaccine candidate against meningococci, in particular serogroup B by enhancing the immunogenicity of NhhA. NID was thereafter recombinantly expressed in E. coli. The NID-expressing E. coli bound to peripheral B lymphocytes that resulted in cellular activation. Furthermore, we also successfully expressed NID on outer membrane vesicles, nanoparticles that are commonly used in meningococcal vaccines. This study thus highlights the applicability of the menigococcal-Moraxella fusion protein NID to be used for specific targeting of vaccine components to the IgD B cell receptor.

Comparative evaluation of simultaneous maxillary sinus floor elevation and implant placement with residual bone heights greater or less than 5 mm.

PURPOSE: Implants can be inserted simultaneously during sinus floor elevation (SFE), or 6 months later, for posterior maxillary rehabilitation. The residual bone height (RBH) is a major factor that affects the type of surgical procedure that will be performed. The aim of this study was to compare the survival rates of implants inserted during one-stage SFE with two different RBHs (< 5 mm and ≥ 5 mm). MATERIALS AND METHODS: This study consisted of implants inserted into an RBH of either < 5 mm or ≥ 5 mm, and the survival of the implants was assessed according to the clinical symptoms of the patients: pain or tenderness during function (or spontaneously), mobility, depth of probing, exudation history, and radiographic bone loss at the final follow-up appointment. The survival rates of the two groups were statistically compared using the Fisher exact test. RESULTS: Fifty-nine consecutive patients (29 women and 30 men) undergoing a one-stage sinus elevation procedure simultaneously with implant insertion were included in this study. Fifty-one implants were placed in the study group (RBH: 1 to 4.9 mm), and 31 implants were placed in the control group (RBH: 5 to 8 mm). The survival rate of the implants in the study group was 94.2% at the 5.4-year follow-up and 95.8% in the control group at the 7.9-year follow-up. There was no statistically significant difference between the groups in terms of the implant survival rate (P = .785). CONCLUSION: The results of this study suggest that SFE with simultaneous implant placement in patients with an RBH < 5 mm can be accomplished, and that the survival rate is similar to that of the one-stage SFE protocol with an RBH of > 5 mm.

[Elizabethkingia meningosepticum bacteremia in a patient with Bardet-Biedl syndrome and chronic renal failure]. / Bardet-Biedl sendromlu kronik böbrek yetmezligi olan bir hastada Elizabethkingia meningosepticum bakteriyemisi.

Elizabethkingia meningosepticum, a gram-negative opportunistic pathogen may cause life-threatening nosocomial infections especially in newborns and immunosuppressive patients. This bacterium has a peculiar antibiotic resistance profile. It is resistant to most of the antibiotics against gram-negative bacteria and susceptible to antibiotics that are used to treat gram-positive bacteria, such as vancomycin and trimethoprim-sulphamethoxazole (SXT). For this reason appropriate treatment of E.meningosepticum infections are based on the proper identification of bacteria. In this report, a case of catheter-related E.meningosepticum bacteremia in a patient with chronic renal failure due to Bardet-Biedl syndrome, a genetic disorder characterized by multiorgan dysfunction, was presented. A 25-year-old male patient with Bardet-Biedl syndrome was admitted to the emergency room with the complaints of high fever with shivers that started the day before. The patient had a femoral dialysis catheter. Venous blood samples drawn at the time of administration were cultured immediately. Two days later, blood cultures which yielded positive signals were passaged onto blood and MacConkey agar plates and after incubation at 37°C for 16 hours, wet-raised colonies with clear margin, gray colour and large size similar to gram-negative bacterial colonies were detected on blood agar medium. No growth was observed on MacConkey agar plate at the end of five days. The isolate was found positive for KOH, oxidase, catalase, urease, esculine and MOI (Motility Indole Ornithine) tests, whereas it was citrate negative. Gram staining revealed faintly stained thin gram-negative bacilli. The isolate was identified as E.meningosepticum by Vitek® 2 system (bioMérieux, USA), and confirmed by sequence analysis of 16S RNA gene region amplified with PCR method. The antibiotic susceptibility profile of the strain was detected by the Vitek 2 system, while vancomycin susceptibility was investigated by Kirby-Bauer disc diffusion method. The isolate was found resistant to ampicillin/sulbactam, piperacillin/tazobactam, ceftazidime, cefepime, meropenem, imipenem, amikacin, gentamicin, netilmicin, levofloxacin, tetracycline, colistin and rifampicin; intermediate to tigecyclin and tetracyclin; susceptible to cefoperazone/sulbactam, ciprofloxacin, levofloxacin, SXT and vancomycin. One gram vancomycin once every four days was administered to the patient, however on the ninth day of the treatment he developed fever again. Blood cultures obtained again yielded E.meningosepticum. After changing his dialysis catheter and extending the vancomycin treatment to 15 days, the patient was discharged with cure. In conclusion, clinicians should consider E.meningosepticum as a possible causative agent of bacteremia non-responsive to the empirical antibiotic regimens and when gram-negative bacteria are isolated from the blood cultures of such patients with underlying diseases. Accurate and prompt identification of E.meningosepticum will allow immediate administration of the specific antibiotic treatment, thereby decreasing the mortality and morbidity rates.

A role for TLRs in Moraxella-superantigen induced polyclonal B cell activation.

A number of microorganisms are capable of binding immunoglobulins (Igs) in a manner, which excludes binding to conventional antigen binding sites. Interaction of such bacterial proteins with surface immunoglobulins leads to polyclonal activation of B-lymphocytes. A recent example is Moraxella catarrhalis that binds to B lymphocytes in an IgD-dependent manner and induces proliferation and differentiation of B lymphocytes leading to the production of unspecific Igs. The activation is mediated by Moraxella IgD binding protein (MID), which specifically binds to both soluble IgD and the IgD B cell receptor (BCR). Besides cross-linking the BCR, whole Moraxella and outer membrane vesicles (OMVs) engage Toll like receptors (TLRs) to further increase the response. TLR activation leads to initiation of signaling pathways, which evoke a proinflammatory response against the invading microbes. Polyclonal B cell activation has in general been implicated in various phenomenons that are detrimental for the host but beneficial for pathogens, for example, autoimmune manifestations and redirection of the immune system.