Expression of bovine annexin A4 in E. coli rescues cytokinesis blocked by beta-lactam antibiotics

Treatment of bacteria with beta-lactam antibiotics can impair the process of cytokinesis, the final step in cell division, leading to the formation of a filamentous form of the bacteria. The expression of a mammalian calcium-dependent, membrane-binding protein, bovine annexin A4, in E. coli was found to reverse the inhibitory effects on cytokinesis of the beta-lactam antibiotics ampicillin, piperacillin, and cephalexin. This novel activity of the annexin was blocked by mutation of calcium binding sites in the annexin, indicating roles for calcium binding to the annexin and the binding of the annexin to membranes in restoring cytokinesis. The filamentous form of the bacteria has been reported to be more resistant to phagocytosis by cells of the immune system in eukaryotic hosts. Therefore, expression of annexins in pathogenic bacteria, by promoting the breakdown of the bacterial filaments, might serve as an adjuvant to enhance the efficacy of beta-lactam antibiotics.