jp0c02609_si_001.pdf (2.84 MB)
Insights into the Polyhexamethylene Biguanide (PHMB) Mechanism of Action on Bacterial Membrane and DNA: A Molecular Dynamics Study
journal contribution
posted on 2020-05-22, 18:38 authored by Shahin Sowlati-Hashjin, Paola Carbone, Mikko KarttunenPolyhexamethylene
biguanide (PHMB) is a cationic polymer with antimicrobial
and antiviral properties. It has been commonly accepted that the antimicrobial
activity is due to the ability of PHMB to perforate the bacterial
phospholipid membrane leading ultimately to its death. In this study,
we show by the means of atomistic molecular dynamics (MD) simulations
that, while the PHMB molecules attach to the surface of the phospholipid
bilayer and partially penetrate it, they do not cause any pore formation
at least within the microsecond simulation times. The polymers initially
adsorb onto the membrane surface via the favorable electrostatic interactions
between the phospholipid headgroups and the biguanide groups and then
partially penetrate the membrane slightly disrupting its structure.
This, however, does not lead to the formation of any pores. The microsecond-scale
simulations reveal that it is unlikely for PHMB to spontaneously pass
through the phospholipid membrane. Our findings suggest that PHMB
translocation across the bilayer may take place through binding to
the phospholipids. Once inside the cell, the polymer can effectively
“bind” to DNA through extensive interactions with DNA
phosphate backbone, which can potentially block the DNA replication
process or activate DNA repair pathways.