In Bacterial Membranes Lipid II Changes the Stability of Pores Formed by the Antimicrobial Peptide Nisin.

Resistance to available antibiotics poses a growing challenge to modern medicine, as this often disallows infections to be controlled. This problem can only be alleviated by the development of new drugs. Nisin, a natural lantibiotic with broad antimicrobial activity, has shown promise as a potential candidate for combating antibiotic-resistant bacteria. However, nisin is poorly soluble and barely stable at physiological pH, which despite attempts to address these issues through mutant design has restricted its use as an antibacterial drug. Therefore, gaining a deeper understanding of the antimicrobial effectiveness, which relies in part on its ability to form pores, is crucial for finding innovative ways to manage infections caused by resistant bacteria. Using large-scale molecular dynamics simulations, we find that the bacterial membrane-specific lipid II increases the stability of pores formed by nisin and that the interplay of nisin and lipid II reduces the overall integrity of bacterial membranes by changing the local thickness and viscosity.

Interconversion between Serum Amyloid A Native and Fibril Conformations.

Overexpression of serum amyloid A (SAA) can lead to a form of amyloidosis where the fibrils are made of SAA fragments, most often SAA1-76. Using Replica Exchange with Tunneling, we study the conversion of a SAA1-76 chain between the folded conformation and a fibril conformation. We find that the basins in the free energy landscape corresponding to the two motifs are separated by barriers of only about 2-3 k B T. Crucial for the assembly into the fibril structure is the salt bridge 26E-34K that provides a scaffold for forming the fibril conformation.