Sulfatide and its synthetic analogues recognition by Moraxella catarrhalis

Moraxella catarrhalis is one of the major pathogens of respiratory and middle ear infections. Attachment of this bacterium to the surface of human pharyngeal epithelial cells is the first step in the pathogenesis of infections. This study revealed that sulfatide might act as a binding molecule for the attachment of M. catarrhalis to human pharyngeal epithelial cells. Furthermore, six different synthetic sulfatides were found to inhibit the attachment of M. catarrhalis significantly at an optimum concentration of 10 μg/ml. Synthetic sulfatides may have the potential to be used as a therapy to prevent M. catarrhalis infections

Restoration of TGF-β signalling reduces tumorigenicity in human lung cancer cells

Members of the transforming growth factor-β (TGF-β) family regulate a wide range of biological processes including cell proliferation, migration, differentiation, apoptosis, and extracellular matrix deposition. Resistance to TGF-β-mediated tumour suppressor function in human lung cancer may occur through the loss of type II receptor (TβRII) expression. In this study, we investigated the expression pattern of TβRII in human lung cancer tissues by RT–PCR and Western blot analyses. We observed downregulation of TβRII in 30 out of 46 NSCLC samples (65%) by semiquantitative RT–PCR. Western blot analyses with tumour lysates showed reduced expression of TβRII in 77% cases. We also determined the effect of TβRII expression in lung adenocarcinoma cell line (VMRC-LCD) that is not responsive to TGF-β due to lack of TβRII expression. Stable expression of TβRII in these cells restored TGF-β-mediated effects including Smad2/3 and Smad4 complex formation, TGF-β-responsive reporter gene activation, inhibition of cell proliferation and increased apoptosis. Clones expressing TβRII showed reduced colony formation in soft-agarose assay and significantly reduced tumorigenicity in athymic nude mice. Therefore, these results suggest that reestablishment of TGF-β signalling in TβRII null cells by stable expression of TβRII can reverse malignant behaviour of cells and loss of TβRII expression may be involved in lung tumour progression

Plasmodium falciparum Adhesion on Human Brain Microvascular Endothelial Cells Involves Transmigration-Like Cup Formation and Induces Opening of Intercellular Junctions

Cerebral malaria, a major cause of death during malaria infection, is characterised by the sequestration of infected red blood cells (IRBC) in brain microvessels. Most of the molecules implicated in the adhesion of IRBC on endothelial cells (EC) are already described; however, the structure of the IRBC/EC junction and the impact of this adhesion on the EC are poorly understood. We analysed this interaction using human brain microvascular EC monolayers co-cultured with IRBC. Our study demonstrates the transfer of material from the IRBC to the brain EC plasma membrane in a trogocytosis-like process, followed by a TNF-enhanced IRBC engulfing process. Upon IRBC/EC binding, parasite antigens are transferred to early endosomes in the EC, in a cytoskeleton-dependent process. This is associated with the opening of the intercellular junctions. The transfer of IRBC antigens can thus transform EC into a target for the immune response and contribute to the profound EC alterations, including peri-vascular oedema, associated with cerebral malaria

A monoclonal antibody reactive with a common epitope of Moraxella (Branhamella) catarrhalis lipopolysaccharides.

A hybrid cell line producing a monoclonal antibody (MAb) against Moraxella (Branhamella) catarrhalis lipopolysaccharide (LPS) was established. The specificity of the MAb 1B12 to purified rough LPSs from six strains of M. catarrhalis was ascertained by enzyme-linked immunosorbent assay (ELISA), competitive-inhibition ELISA, and immunoblotting. MAb 1B12 bound to live bacterial cells and culture supernatants from a total of 34 strains of M. catarrhalis, including 12 strains with different LPS serotypes. No cross-reactions with smooth and rough LPSs from selected enterobacterial and nonenterobacterial strains, with other respiratory pathogens, or with Neisseria species were observed. These data suggest that MAb 1B12 recognizes a common epitope of M. catarrhalis LPS which differs from serotype determinants

Comparison of Antibiotic Resistance and Serotype Composition of Carriage and Invasive Pneumococci among Bangladeshi Children: Implications for Treatment Policy and Vaccine Formulation

The nasopharyngeal carriage of Streptococcus pneumoniae is thought to pose a risk for invasive pneumococcal diseases, and the evaluation of carriage strains is thus often used to inform antibiotic treatment and vaccination strategies for these diseases. In this study, the age-specific prevalences, resistance to antibiotics, and serotype distributions of 1,340 carriage strains were analyzed and compared to 71 pneumococcal strains isolated from the cerebrospinal fluid of children under 5 years old with meningitis. Overall, the nasal carriage rate was 47%. One-fourth (26%) of the infants under 1 month of age and one-half (48%) of the infants under 12 months of age were colonized with S. pneumoniae. Rural children were colonized earlier than those from urban areas. Approximately one-fourth and one-half of the cases of pneumococcal meningitis occurred in the first 3 and 6 months of life, respectively. The respective rates of resistance for carriage and meningitis strains to penicillin (7 and 3%), cotrimoxazole (77 and 69%), and erythromycin (2 and 1%) were similar, whereas chloramphenicol resistance was lower among carriage strains (3%) than among meningitis strains (15.5%). The predominant serogroups of carriage and invasive isolates were variable and widely divergent. Thus, hypothetical 7-, 9-, and 11-valent vaccines, based on the predominant carriage strains of the present study, would cover only 23, 26, and 30%, respectively, of the serotypes causing meningitis. Further, currently available 7-, 9-, and 11-valent vaccines would protect against only 26, 43, and 48%, respectively, of these meningitis cases. In conclusion, while the surveillance of carriage strains for resistance to antibiotics appears useful in the design of empirical treatment guidelines for invasive pneumococcal disease, data on the serotypes of carriage strains have limited value in vaccine formulation strategies, particularly for meningitis cases