Surface display of proteins by Gram-negative bacterial autotransporters

Expressing proteins of interest as fusions to proteins of the bacterial envelope is a powerful technique with many biotechnological and medical applications. Autotransporters have recently emerged as a good tool for bacterial surface display. These proteins are composed of an N-terminal signal peptide, followed by a passenger domain and a translocator domain that mediates the outer membrane translocation of the passenger. The natural passenger domain of autotransporters can be replaced by heterologous proteins that become displayed at the bacterial surface by the translocator domain. The simplicity and versatility of this system has made it very attractive and it has been used to display functional enzymes, vaccine antigens as well as polypeptides libraries. The recent advances in the study of the translocation mechanism of autotransporters have raised several controversial issues with implications for their use as display systems. These issues include the requirement for the displayed polypeptides to remain in a translocation-competent state in the periplasm, the requirement for specific signal sequences and "autochaperone" domains, and the influence of the genetic background of the expression host strain. It is therefore important to better understand the mechanism of translocation of autotransporters in order to employ them to their full potential. This review will focus on the recent advances in the study of the translocation mechanism of autotransporters and describe practical considerations regarding their use for bacterial surface display

Suivi immuno-virologique et thérapeutique de l'infection à VIH chez des enfants suivis au CHU pédiatrique de Ouagadougou (collaboration ESTHER)

L accès au TAR pour tous, demeure un défi majeur et un enjeu stratégique de la lutte contre le VIH. Défi majeur car le prix des traitements reste inabordable pour la grande majorité de ceux qui en ont besoin. Enjeu stratégique car traiter permet de réduire la mortalité des personnes infectées, mais permet aussi d agir sur l incidence de la maladie en diminuant le nombre de nouvelles contaminations, notamment par la réduction du risque de transmission mère-enfant. Dans le cadre du programme ESTHER, les laboratoires du CHU pédiatrique Charles De Gaulle de Ouagadougou et celui du CHU Charles Nicolle travaillent dans le but d'améliorer la prise en charge des enfants infectés par le VIH. L objectif de notre travail a été de décrire les caractéristiques immuno-virologiques et thérapeutiques et de l infection à VIH chez les enfants suivis au CHU pédiatrique de Ouagadougou, et de préciser les aspects génotypiques des virus infectant ces malades Nos résultats montrent que les patients traités ont un taux de suppression virologique de près de 70%, et ce quelle que soit la ligne considérée. Comme attendu, l'état immunologique des patients traités était meilleur que celui des patients non traités. Chez les patients traités en situation d'échec virologique, les mutations de résistance aux INTI montrent une forte prévalence de la M184V et des TAM's. Les mutations de résistance aux INNTI sont nombreuses et confèrent une résistance aux INNTI de première génération très importante. La grande majorité des mutations de résistance aux IP sont des mutations mineures ou polymorphiques.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Misidentification of a Hepatitis C Virus (HCV) recombinant form leading to treatment failure with new direct acting antivirals

International audienc

Polyomaviruses KI and WU in Immunocompromised Patients with Respiratory Disease

Polyomaviruses KI (KIPyV) and WU (WUPyV) were recently identified, mainly in respiratory specimens from children. Among 200 patients with respiratory disorders admitted to Saint Louis Hospital, Paris, France, KIPyV was detected in 8% and WUPyV in 1%. KIPyV was significantly more frequent among human stem cell transplant patients (17.8% vs. 5.1%; p = 0.01)

HIV-1/M+O INTERGROUP DUAL INFECTIONS AND ASSOCIATED HIV-MO RECOMBINANTS IN FRANCE FROM 2004 TO 2014

International audienc

Serologic Evidence of Frequent Human Infection with WU and KI Polyomaviruses

WU and KI polyomavirus infections are widespread

KI and WU Polyomaviruses and CD4+ Cell Counts in HIV-1–infected Patients, Italy

To investigate an association between KI and WU polyomavirus (KIPyV and WUPyV) infections and CD4+ cell counts, we tested HIV-1–positive patients and blood donors. No association was found between cell counts and virus infections in HIV-1–positive patients. Frequency of KIPyV infection was similar for both groups. WUPyV was more frequent in HIV-1–positive patients

Inhibition of Casein kinase-2 induces p53-dependent cell cycle arrest and sensitizes glioblastoma cells to tumor necrosis factor (TNFα)-induced apoptosis through SIRT1 inhibition

Glioblastoma multiforme (GBM) are resistant to TNFα-induced apoptosis and blockade of TNFα-induced NF-κB activation sensitizes glioma cells to apoptosis. As Casein kinase-2 (CK2) induces aberrant NF-κB activation and as we observed elevated CK2 levels in GBM tumors, we investigated the potential of CK2 inhibitors (CK2-Is) - DRB and Apigenin in sensitizing glioma cells to TNFα-induced apoptosis. CK2-Is and CK2 small interfering RNA (siRNA) reduced glioma cell viability, inhibited TNFα-mediated NF-κB activation, and sensitized cell to TNFα-induced apoptosis. Importantly, CK2-Is activated p53 function in wild-type but not in p53 mutant cells. Activation of p53 function involved its increased transcriptional activation, DNA-binding ability, increased expression of p53 target genes associated with cell cycle progression and apoptosis. Moreover, CK2-Is decreased telomerase activity and increased senescence in a p53-dependent manner. Apoptotic gene profiling indicated that CK2-Is differentially affect p53 and TNFα targets in p53 wild-type and mutant glioma cells. CK2-I decreased MDM2-p53 association and p53 ubiquitination to enhance p53 levels. Interestingly, CK2-Is downregulated SIRT1 activity and over-expression of SIRT1 decreased p53 transcriptional activity and rescued cells from CK2-I-induced apoptosis. This ability of CK2-Is to sensitize glioma to TNFα-induced death via multiple mechanisms involving abrogation of NF-κB activation, reactivation of wild-type p53 function and SIRT1 inhibition warrants investigation