The single confocal image does not unambiguously prove the internalization of the PLGA NPs in the cells, which could also be associated to the cell membrane.
Since the HC may be associated to the cell membrane [31], we reasoned that α-cleavage may be affected by the distance between the cleavage site and the cell membrane.
The above data favor a model in which the LukS-PV signal peptide after cleavage by the signal peptidase is released outside the cytoplasmic membrane but remains associated to the cell surface and confers adhesion to heparan sulfates.
Hence, we propose a simple non-linear regression model as a novel analytical tool to distinguish drug specific gene induction from the effect of the time changed gene expression variation associated to the cell cycle.
SNP analysis of mononuclear cells from the patient bone marrow and the established LM1 cell line detected a number of changes associated to the cell line including chromosomal gain in 1q, 3q13.31-qtel, 8, 11p13 and 19p as well as chromosomal loss in 1p, 2q22.1-qtel, 4q12-qtel, 7q36.3, 10, 13q11-q21.32, 13q21.33-q22.2, 17ptel-13p13.1, 19q22, 19q, and Xp21.1-q21.31, Xq21.33-q22.1, Xq22.3-qtel.
This result is in agreement with a previous report describing the contribution of SrtA to pili production in GBS [29] and conceivably explained by the fact that the pili subunits are assembled by the pilin polymerase SrtF irrespective of the presence of SrtA, remaining transiently associated to the cell wall.
Our data suggests that after its cleavage by signal peptidase, the signal peptide is released from the membrane and associates to the cell wall through its unique C-terminus sequence, while its highly positively charged N-terminus is exposed on the bacterial surface, allowing its interaction with extracellular matrix-associated HS.
