Magnesium And Calcium Ions Are Membrane-Active Against Stationary-Phase Staphylococcus Aureus

The emergence and spread of antibiotic-resistant bacteria necessitate the development of novel antibacterial agents. Antimicrobial peptides (AMPs) from the innate immunity and their synthetic mimics act by destabilizing bacterial cell membranes and are thus widely viewed as a promising source of novel anti-infective Pharmaceuticals. On the other hand, heavy metal cations, including Cu2+, Ag+, Hg2+, Zn2+ and Cd2+, have demonstrated antibacterial ability. Limestone or shells rich in calcium and magnesium also show activity against Gram-negative and -positive bacteria. Note that solutions of calcium chloride and magnesium chloride can deform liposomes rich cardiolipin (CL), lipids present at high content in the cellular membranes of Staphylococcus aureus—a notorious pathogenic bacteria, into an inverted hexagonal phase rich in water channels. Hence we examine whether solutions of calcium chloride and magnesium chloride on mM scale can disturb bacterial cell membranes of Staphylococcus aureus and eventually kill the bacteria. Our results show that both calcium and magnesium ions at ～40mM kill ～60% inoculated Staphylococcus aureus cells in stationary phase and effectively deform CL-rich membrane vesicles, a simple but useful model for mimicking the Staphylococcus aureus cellular membranes, indicative of membrane-activity. Intriguingly, the survivals of E. coli (a Gram-negative bacteria) and B. subtilis (a Gram-positive bacteria) cells are barely affected in similar assays, indicative of narrow-spectrum activity. Moreover, both calcium and magnesium ions at ～40mM are not hemolytic to mouse red blood cells, indicative of lack of toxicity. With membrane-activity against Staphylococcus aureus cells in stationary phase while lacking toxicity, solutions of calcium chloride and magnesium chloride may be a potential narrow-spectrum antimicrobial especially for the looming post-antibiotic era. Bacteria is harmful to our human beings. And then a lot of antibacterial agents are found like antibiotics. But after the abusing of antibiotics, bacteria are being more resistance and getting harder to be killed by traditional agents. Under this condition, new antibacterial agents must be found.