What is the mechanism of Polymyxin B Sulfate?

Polymyxin B sulfate is a potent antibiotic that specifically targets Gram-negative bacteria. Its mode of action is unique and highly effective, making it an essential tool in the treatment of infections caused by these bacteria. Understanding the mechanism of Polymyxin B sulfate requires delving into the intricate details of how it interacts with bacterial cells.

The primary mechanism of action for Polymyxin B sulfate involves disrupting the structure and function of the bacterial cell membrane. This antibiotic is cationic (positively charged), which allows it to interact strongly with the negatively charged components of the outer membrane of Gram-negative bacteria. The key target within this membrane is lipopolysaccharides (LPS), which are vital for maintaining the integrity and function of the bacterial cell envelope.

Upon administration, Polymyxin B molecules bind to the lipid A component of LPS. This binding displaces divalent cations such as calcium and magnesium that typically stabilize the LPS structure by forming cross-bridges between phosphate groups on lipid A molecules. The displacement of these cations leads to a destabilization of the LPS layer. As a result, the outer membrane becomes more permeable.

The increased permeability is critical because it allows Polymyxin B to penetrate further into the bacterial cell envelope. Once the outer membrane integrity is compromised, Polymyxin B reaches the inner membrane, also known as the cytoplasmic membrane. Here, it inserts itself into the phospholipid bilayer, interacting with the phospholipids and causing further disruption.

By embedding itself into the inner membrane, Polymyxin B creates pores or channels. These pores disrupt the membrane's barrier function and lead to leakage of essential cellular contents, such as ions, nucleotides, and other small molecules. The loss of these cellular contents is lethal to the bacteria as it disrupts metabolic functions, energy production, and overall cellular homeostasis.

Moreover, the interaction of Polymyxin B with the inner membrane also induces oxidative stress within the bacterial cell. This stress results from the generation of reactive oxygen species (ROS), which cause further damage to cellular components, including proteins, lipids, and DNA.

In summary, the mechanism of Polymyxin B sulfate is primarily based on its interaction with the bacterial membranes. It initially binds to the LPS in the outer membrane, causing destabilization and increased permeability. Subsequently, it penetrates and disrupts the inner membrane by forming pores, leading to the leakage of cellular contents and ultimately bacterial cell death. This multifaceted attack on bacterial membranes makes Polymyxin B sulfate a highly effective antibiotic against Gram-negative pathogens.