Antibiofilm Activity of PEGylated Branched Polyethylenimine

Abstract

Biofilm formation is an adaptive resistance mechanism that pathogens employ to survive in the presence of antimicrobials. Pseudomonas aeruginosa is an infectious Gramnegative bacterium whose biofilm allows it to withstand antimicrobial attack and threaten human health. Chronic wound healing is often impeded by P. aeruginosa infections and the associated biofilms. Previous findings demonstrate that 600 Da branched polyethylenimine (BPEI) can restore β-lactam potency against P. aeruginosa and disrupt its biofilms. Toxicity concerns of 600 Da BPEI are mitigated by covalent linkage with low-molecularweight polyethylene glycol (PEG), and, in this study, PEGylated BPEI (PEG350-BPEI) was found exhibit superior antibiofilm activity against P. aeruginosa. The antibiofilm activity of both 600 Da BPEI and its PEG derivative was characterized with fluorescence studies and microscopy imaging. We also describe a variation of the colony biofilm model that was employed to evaluate the biofilm disruption activity of BPEI and PEG-BPEI.

Photodynamic Activity of Chlorophyllin and Polyethylenimine on Pseudomonas aeruginosa Planktonic, Biofilm and Persister Cells

“…However, more than CHL/PEI 500/100 µg mL −1 was required to eradicate the bacteria in the colony biofilm. Similarly, Panlilio and colleagues [52] proved that P. aeruginosa biofilm can be disrupted via PEI linked with polyethylene glycol. The cationic nature of the PEI most probably destabilizes the biofilm components such as the eDNA, proteins and extracellular polymeric matrix via electrostatic interaction [52].…”

“…Similarly, Panlilio and colleagues [52] proved that P. aeruginosa biofilm can be disrupted via PEI linked with polyethylene glycol. The cationic nature of the PEI most probably destabilizes the biofilm components such as the eDNA, proteins and extracellular polymeric matrix via electrostatic interaction [52]. Therefore, PEI could help the deeper penetration of the CHL in order to exert its action against the biofilm life forms.…”

Neutralizing Staphylococcus aureus PAMPs that Trigger Cytokine Release from THP-1 Monocytes

“…BPEI, along with the safer derivative PEG-BPEI, exhibit several beneficial properties − These compounds have shown the potential to enhance the uptake of drugs, reduce barriers to drug influx, and counteract antibiotic resistance mechanisms. Moreover, BPEI and PEG-BPEI potentiators possess an additional advantage in their ability to disrupt biofilms formed by Staphylococci, P.…”

“…Moreover, BPEI and PEG-BPEI potentiators possess an additional advantage in their ability to disrupt biofilms formed by Staphylococci, P. aeruginosa, and carbapenem-resistant Enterobacteriaceae bacteria expressing KPC and NDM-1. − …”

“… − ,− ,− However, the toxicity concerns arising from the presence of primary amines 600 Da BPEI are significant and need to be addressed. The in vivo toxicity concerns are resolved by covalently conjugating a low-molecular-weight polyethylene glycol (350 MW PEG) moiety to 600 Da BPEI, resulting in PEG-BPEI (Figure bottom). ,− Additionally, we have shown that the PEGylated derivative possesses the potentiator characteristics of BPEI against the MDR strains and their biofilms. ,− Regardless of the BPEI ability to facilitate the uptake of drugs and lower drug influx barriers as an antibiotic potentiator against bacterial biofilms and planktonic cells, therapeutic benefits of 600 Da BPEI and PEG-BPEI can be expanded. In this work, we continue to investigate 600 Da BPEI and its PEGylated derivative as anti-PAMP molecules to help mitigate the overproduction of inflammatory response.…”