The nonrandom binding distribution of Streptococcus pneumoniae to type II pneumocytes in culture is dependent on the relative distribution of cells among the phases of the cell cycle

Abstract

The adherence of Streptococcus pneumoniae to epithelial (A549) lung cells was studied and the bacterial binding distribution was found to be nonrandom (non-Gaussian). Analysis of the dependency of bacterial binding on the cell cycle of A549 cells revealed that approximately 1.8 times more bacteria bind to G2 cells than to G0-G1 phase cells. Furthermore, bacterial binding curves exhibited a plateau of binding to G2 cells at a normalized bacteria to cell ratio approximately 1.8 times larger than that at which the plateau of binding to G0-G1 cell was observed. Since G2 cells are on average 1.4-1.8 times larger than G0-G1 cells, the results indicate that bacterial binding is proportional to cell size and not to the preferential binding (higher affinity) of bacteria to A549 cells in the G2 phase. Finally, the non-Gaussian distribution of bacterial binding could be mathematically modeled by a linear combination of three Gaussian distributions each representing bacterial binding to cells in a particular phase of the cell cycle (G0-G1, S, and G2-M). Because the Gaussian function contains a term that takes into account the relative number of cells in each of the phases, this last result implies that the overall (non-Gaussian) binding distribution (and hence the median of bacterial binding) can be highly sensitive to the relative proportion of cells in the various phases of the cell cycle.