Disrupting the plasma membrane causes rapid depolarization, resulting in a loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis, which leads to bacterial cell death. There are several types of antibiotics that function by disrupting or injuring the plasma membrane. One example is daptomycin, a cyclic lipopeptide that binds to bacterial plasma membranes, entering the phospholipid bilayers and causing a loss of membrane potential and redirecting proteins essential for cell division and cell wall synthesis (Figure 1). Before these effects were discovered, daptomycin was first shown to interfere with peptidoglycan synthesis. Resistance to daptomycin is rare but has been associated with point mutations in mprF, whose gene product controls the addition of a lysine to membrane phosphatidylglycerol to produce lysylphosphatidylglycerol. Indeed, the composition of the cell membrane influences the antimicrobial activity of cationic antimicrobial peptides. Alterations of the histidine kinase YycG, which is thought to be involved in cell permeability, have also been implicated in daptomycin resistance.
Figure 1: Antibiotics interfere with plasma membrane function.
