Phosphatidylglycerol (PG) is the most abundant phospholipid in Gram-positive cell membranes . PG can exist in its native form or be esterified to an amino acid, typically alanine or lysine . It is a negatively charged phospholipid with two acyl chains (typically 16-18 carbons in length) and a headgroup characterized by two hydroxyl groups and the anionic phosphate group . PG interacts with cations [235], particularly divalent ones like calcium , which can bridge negatively charged membrane components and facilitate bacterial aggregation by neutralizing the cell surface charge . Calcium presence also plays a role in the efficacy of AMPs such as daptomycin . The modification of PG with alanyl-or lysyl-groups increases the amount of positive charges at the surface (alanyl-PG is zwitterionic, lysyl-PG carries a +1 net charge). For example, in S. aureus, lysyl-PG is more abundant during the logarithmic growth phase [239], increasing resistance to cationic AMPs by the increased surface charge and by promoting tighter membrane packing .