Neisseria meningitidis Differentially Controls Host Cell Motility through PilC1 and PilC2 Components of Type IV Pili

Neisseria meningitidis is a strictly human pathogen that has two facets since asymptomatic carriage can unpredictably turn into fulminant forms of infection. Meningococcal pathogenesis relies on the ability of the bacteria to break host epithelial or endothelial cellular barriers. Highly restrictive, yet poorly understood, mechanisms allow meningococcal adhesion to cells of only human origin. Adhesion of encapsulated and virulent meningococci to human cells relies on the expression of bacterial type four pili (T4P) that trigger intense host cell signalling. Among the components of the meningococcal T4P, the concomitantly expressed PilC1 and PilC2 proteins regulate pili exposure at the bacterial surface, and until now, PilC1 was believed to be specifically responsible for T4P-mediated meningococcal adhesion to human cells. Contrary to previous reports, we show that, like PilC1, the meningococcal PilC2 component is capable of mediating adhesion to human ME180 epithelial cells, with cortical plaque formation and F-actin condensation. However, PilC1 and PilC2 promote different effects on infected cells. Cellular tracking analysis revealed that PilC1-expressing meningococci caused a severe reduction in the motility of infected cells, which was not the case when cells were infected with PilC2-expressing strains. The amount of both total and phosphorylated forms of EGFR was dramatically reduced in cells upon PilC1-mediated infection. In contrast, PilC2-mediated infection did not notably affect the EGFR pathway, and these specificities were shared among unrelated meningococcal strains. These results suggest that meningococci have evolved a highly discriminative tool for differential adhesion in specific microenvironments where different cell types are present. Moreover, the fine-tuning of cellular control through the combined action of two concomitantly expressed, but distinctly regulated, T4P-associated variants of the same molecule (i.e. PilC1 and PilC2) brings a new model to light for the analysis of the interplay between pathogenic bacteria and human host cells

Persisting Mixed Cryoglobulinemia in Chikungunya Infection

Chikungunya virus is present in tropical Africa and Asia and is transmitted by mosquito bites. The disease is characterized by fever, headache, severe joint pain and transient skin rash for about a week. Most patients experience persisting joint pain and/or stiffness for months to years. In routine practice, diagnosis is based upon serology. Since 2004 there has been an ongoing giant outbreak of Chikungunya fever in East Africa, the Indian Ocean Islands, India and East Asia. In parallel, more than 1,000 travelers were diagnosed with imported Chikungunya infection in most developed countries. Considering the clinical features of our patients (joint pain), we hypothesized that cryoglobulins could be involved in the pathophysiology of the disease as observed in chronic hepatitis C infection. Cryoglobulins, which are immunoglobulins that precipitate when temperature is below 37°C, can induce rheumatic and vascular disorders. From April 2005 through May 2007, we screened all patients with possible imported Chikungunya infection for cryoglobulins. They were present in over 90% of patients, and possibly responsible for the unexpected false negativity of serological assays. Cryoglobulin frequency and levels decreased with time in recovering patients

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

La théorie variation des rayons complexes pour le calcul des vibrations moyennes fréquences

A new approach named the "Variational Theory of Complex Rays" is introduced for computing the vibrations of elastic structures weakly damped in the medium frequency range. Emphasis has been placed here on the most fundamental aspects. The effective quantities (elastic energy, vibration intensity ...) are evaluated after computing a small system of equations which does not derive from a finite element dicretization of the structure. Numerical examples related to plates show the interest and the possibilities ofthe VTRC

Recurrent pneumococcal meningitis in a splenectomised HIV-infected patient

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus pneumoniae </it>is a major cause of human disease, especially in pre-school children and elderly people, as well as in special risk groups such as asplenic, antibody deficient patients, or presenting disruption of natural barriers. The occurrence of pneumococcal disease has increased with the onset of the HIV epidemic and the emergence of drug-resistance.</p> <p>Case presentation</p> <p>We report the case of an HIV-1-infected patient who experienced three episodes of recurrent pneumococcal meningitis over a 4-year period, despite chemoprophylaxis and capsular vaccination.</p> <p>Conclusions</p> <p>Efficacy of anti-pneumococcal chemoprophylaxis and vaccination in HIV-infected patients are discussed in the light of this particular case.</p