eDNA Inactivation and Biofilm Inhibition by the Polymeric Biocide Polyhexamethylene Guanidine Hydrochloride (PHMG-Cl)

Abstract

The choice of effective biocides used for routine hospital practice should consider the role of disinfectants in the maintenance and development of local resistome and how they might affect antibiotic resistance gene transfer within the hospital microbial population. Currently, there is little understanding of how different biocides contribute to eDNA release that may contribute to gene transfer and subsequent environmental retention. Here we investigated how different biocides affected the release of eDNA from mature biofilms of two opportunistic model strains Pseudomonas aeruginosa ATCC 27853 (PA) and Staphylococcus aureus ATCC 25923 (SA) and contribute to the hospital resistome in the form of surface and water contaminants and dust particles. The effect of four groups of biocides including alcohols, hydrogen peroxide, quaternary ammonium compounds, and polymeric guanidines were evaluated using PA and SA biofilms. Most biocides, except for PHMG-Cl and 70% ethanol, caused substantial eDNA release and PHMG-Cl was found to block biofilm development when used at concentrations of 0.5% and 0.1%. This might be associated with the formation of DNA-PHMG-Cl complexes as PHMG-Cl is predicted to bind to AT base pairs by molecular docking assays. PHMG-Cl was found to bind high molecular DNA and plasmid DNA and continued to inactivate DNA on surfaces even after four weeks. PHMG-Cl also effectively inactivated biofilm-associated antibiotic resistance gene eDNA released by a pan-drug-resistant Klebsiella strain which demonstrates the potential of PHMG-Cl as a new surface-active agent to combat the spread of antibiotic resistance in hospital settings.

A combination therapy strategy for treating antibiotic resistant biofilm infection using a guanidinium derivative and nanoparticulate Ag(0) derived hybrid gel conjugate

“…22 A recent reports also tend to suggest that polyhexamethylene guanidine hydrochloride (PHMG-Cl) could adversely affect the biofilm-associated antibiotic-resistant eDNA release by Klebsiella strain-a key factor for a pan-drug-resistant Klebsiella strain. 93 These have helped us in developing Ag(0) N.P.s (with positive surface charges) stabilized in a hydrogel matrix of cationic guanidinium ion derivatives.…”

“…91,92 PHMG-Cl might form a DNA-PHMG-Cl complex, bind to AT base pairs by molecular docking, and inactivate biolm-associated antibiotic-resistant eDNA release by Klebsiella strain. 93 Guanidinium-based Ionic Covalent Organic Nanosheets (iCONs) were earlier shown to have a bactericidal effect against both Gram +ve (S. aureus) and Gram Àve (E. coli) bacteria. Electrostatic interactions between positively charged iCONs and the negatively charged phospholipid bilayer of the bacterial membrane were speculated to be the reason for the bactericidal effect of guanidinium-based iCONs.…”