Antibiotics are a class of secondary metabolites produced from microorganisms, animals or plants. Some of them exhibit anti-bacterial, anti-fungal, anthelmintic, anti-tumor or immunosuppressive activities with a wealth of structural classes. They are the most important type of antibacterial agent for fighting bacterial infections. Among them, calcium-dependent antibiotics are a small family of N-acylated cyclic peptides that require calcium for antibacterial activity. Known members of this family contain a conserved Asp-X-Asp-Gly motif that is thought to facilitate calcium binding. However, antibiotic resistance is also a growing threat to global public health.
Malacidin A is a calcium-dependent lipopeptide antibiotic with activity against multidrug-resistant Gram-positive pathogens.
In addition, Malacidin A is a cyclic lipopeptide containing 8 amino acid macrocycles and polyunsaturated lipid. This compound belongs to a family of calcium-dependent lipopeptide antibiotics that exhibit their activity upon binding to calcium ions. Particularly, Malacidin A is highly active against many antibiotic-resistant pathogens, particularly Gram-positive bacteria. For example, topical administration of Malacidin A is successful in sterilizing Methicillin-resistant Staphylococcus aureus (MRSA) infected wounds in a rat model. At 24 and 72 hours post-infection, Malacidin A treatment results in no observed bacterial burdens in the wounds. Meanwhile, Malacidin A does not show significant toxicity or hemolytic activity in mammalian cells. Furthermore, S. aureus treated with Malacidin A accumulates the cell wall precursor undecaprenyl-N-acetylmuramic acid-pentapeptide (UDP-MurNAc-pentapeptide). This signaled that the target of Malacidin A, lies downstream of UDP-MurNAc-pentapeptide formation. Moreover, Malacidin A appears to interact with lipid II in a calcium-dependent manner.
To sum up, Malacidin A is a calcium-dependent antibiotic with activity against multidrug-resistant Gram-positive pathogens.