The broad-spectrum antimicrobial biocide polyhexamethylene biguanide (PHMB; polyhexanide) kills bacteria, fungi, parasites and certain viruses with a high therapeutic index. PHMB is composed of repeating basic biguanidine units connected by hexamethylene hydrocarbon chains, providing a cationic and amphipathic structure. Resistance to PHMB has not been reported.
Kantaraja Chindera and Coll. conducted this study in which they showed how the PHMB can kill bacterials.
Antibacterial activity of PHMB is due to membrane disruption, as widely reported. PHMB’s primary target is not bacterial cell barriers, or not exclusively cell barriers, then it likely acts internally, and this would require cell entry. PHMB arrests cell division and condenses bacterial chromosomes.
If PHMB condenses bacterial chromosomes inside cells, this could occur via direct or indirect effects on DNA. Kantaraja Chindera and Coll suspected direct effects, because PHMB has been shown to bind to DNA fragments in vitro. They decided to examine the DNA binding properties of PHMB using isolated E. coli chromosomal DNA. The results of these experiments indicate that PHMB binds directly to DNA. The antibacterial effects of PHMB are suppressed by a dsDNA ligand.
A chromosome condensation model for the antibacterial action of PHMB (Fig. 5a) can explain how PHMB kills bacteria. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes.
Authors Kantaraja Chindera, Manohar Mahato, Ashwani Kumar Sharma, Harry Horsley, Klaudia Kloc-Muniak, Nor Fadhilah Kamaruzzaman, Satish Kumar, Alexander McFarlane, Jem Stach, Thomas Bentin, and Liam Good
Newspaper Sci Rep. 2016; 6: 23121.