Polymyxin B & LPS: Mechanism of Action?

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The discussion centers on the mechanism by which polymyxin antibiotics interact with bacterial outer membranes, specifically focusing on their binding to lipopolysaccharides (LPS) and subsequent effects. Various sources highlight that polymyxins first bind to the outer membrane of bacteria like E. coli and Salmonella typhimurium through LPS, leading to disruption of the membrane barrier. This disruption is attributed to the antibiotics' detergent-like action, which increases cell permeability and can ultimately result in cell death. The literature reviewed spans from 1987 to 2002, indicating a lack of consensus on the exact mechanism, particularly regarding the transition from outer membrane interaction to action on the cytoplasmic membrane. The discussion also mentions that polymyxins may affect the inner nuclear membrane, contributing to cell death through membrane disruption and potential chromatin destruction. The search for a more detailed understanding of polymyxins' mechanisms remains ongoing, with participants seeking additional literature for clarification.
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Does anyone know the exact mechanism by which polymyxin arrives at the outer cell membrane after binding to LPS? The best source I have states that "it first binds to the outer membrane of E. coli or Salmonella typhimurium, presumably by binding to LPS, and then goes through the outer membrane by dsirupting this membrane barrier". That was published in 1987. Another source I have states that "Polymyxin B, similarly, disorganizes the OM" (outer membrane) "but this it does by binding to the LPS. The actual site of action is the cytoplasmic membrane to which it gets bound through its affinity for phospholipids". This was published in 1994, and no, that sentence isn't a typo (on my part anyway). My last source says "these antibiotics insert into bacterial membranes by interacting with lipopolysaccharides and the phospholipids in the outer membrane, producing increased cell permeability and eventual cell death." This was published in 2002. I can't find a conclusive mechanism here. Any thoughts on some literature that might help clarify this? Thanks!
 
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It's what i found: Polymyxins "affect the cell membrane by detergent action" and I found this

Penetration and poration of the inner nuclear membrane will result in cell death by membrane disruption, possible chromatin destruction, and the usurping of Gibbs-Donnon equilibrium. Many antibiotics such as Protegrin, Gramicidin, Nystatin, and Polymyxin B kill microbial cells by this mechanism.

From there http://www.tadpromotion.com/defmech.htm

From what i read polymyxins appears to disrupt the ctoplasmic membrane.
 
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Thank you Ian. Your input is always very much appreciated.:smile: I have just been looking for the detailed mechanism of the antibiotic on the membrane itself and can't find exactly what I am looking for.
 

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