Streptococcus pneumoniae Cell-Wall-Localized Phosphoenolpyruvate Protein Phosphotransferase Can Function as an Adhesin: Identification of Its Host Target Molecules and Evaluation of Its Potential as a Vaccine.

In Streptococcus pneumonia, phosphoenolpyruvate protein phosphotransferase (PtsA) is an intracellular protein of the monosaccharide phosphotransferase systems. Biochemical and immunostaining methods were applied to show that PtsA also localizes to the bacterial cell-wall. Thus, it was suspected that PtsA has functions other than its main cytoplasmic enzymatic role. Indeed, recombinant PtsA and anti-rPtsA antiserum were shown to inhibit adhesion of S. pneumoniae to cultured human lung adenocarcinoma A549 cells. Screening of a combinatorial peptide library expressed in a filamentous phage with rPtsA identified epitopes that were capable of inhibiting S. pneumoniae adhesion to A549 cells. The insert peptides in the phages were sequenced, and homologous sequences were found in human BMPER, multimerin1, protocadherin19, integrinß4, epsin1 and collagen type VIIα1 proteins, all of which can be found in A549 cells except the latter. Six peptides, synthesized according to the homologous sequences in the human proteins, specifically bound rPtsA in the micromolar range and significantly inhibited pneumococcal adhesion in vitro to lung- and tracheal-derived cell lines. In addition, the tested peptides inhibited lung colonization after intranasal inoculation of mice with S. pneumoniae. Immunization with rPtsA protected the mice against a sublethal intranasal and a lethal intravenous pneumococcal challenge. In addition, mouse anti rPtsA antiserum reduced bacterial virulence in the intravenous inoculation mouse model. These findings showed that the surface-localized PtsA functions as an adhesin, PtsA binding peptides derived from its putative target molecules can be considered for future development of therapeutics, and rPtsA should be regarded as a candidate for vaccine development.

High content of Langerhans cells in malignant lymphoma--incidence and significance.

We describe 25 patients, 14 with classical Hodgkin lymphoma and 11 with non-Hodgkin lymphoma, in all of whom an excess of Langerhans cells was evident. Except for the first three cases, in which the excess of Langerhans cells was identified on routine slides, the remaining cases were disclosed by actively investigating lymphomas with excess of CD68+ histiocytes and performing CD1a and S-100 protein immunostains. Although no clonality study was performed on the Langerhans cells, we endorse the view which states that in the above association, the Langerhans cells are polyclonal. Fourteen cases of Hodgkin lymphoma with a large number of Langerhans cells were identified in a cohort of 231 classical Hodgkin lymphomas. We compared the features of classical Hodgkin lymphoma with abundant Langerhans cells with those without Langerhans cells. Our analysis reveals that Hodgkin lymphoma with Langerhans cell excess shows greater LMP1/EBV expression (P = .007) and lower p53 expression (P = .042) in the Hodgkin-Reed-Sternberg cells but is not associated with a poorer outcome.