Broad Spectrum Antibacterial and Antifungal Polymeric Paint Materials: Synthesis, Structure–Activity Relationship, and Membrane-Active Mode of Action

Abstract

Microbial attachment and subsequent colonization onto surfaces lead to the spread of deadly community-acquired and hospital-acquired (nosocomial) infections. Noncovalent immobilization of water insoluble and organo-soluble cationic polymers onto a surface is a facile approach to prevent microbial contamination. In the present study, we described the synthesis of water insoluble and organo-soluble polymeric materials and demonstrated their structure-activity relationship against various human pathogenic bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and beta lactam-resistant Klebsiella pneumoniae as well as pathogenic fungi such as Candida spp. and Cryptococcus spp. The polymer coated surfaces completely inactivated both bacteria and fungi upon contact (5 log reduction with respect to control). Linear polymers were more active and found to have a higher killing rate than the branched polymers. The polymer coated surfaces also exhibited significant activity in various complex mammalian fluids such as serum, plasma, and blood and showed negligible hemolysis at an amount much higher than minimum inhibitory amounts (MIAs). These polymers were found to have excellent compatibility with other medically relevant polymers (polylactic acid, PLA) and commercial paint. The cationic hydrophobic polymer coatings disrupted the lipid membrane of both bacteria and fungi and thus showed a membrane-active mode of action. Further, bacteria did not develop resistance against these membrane-active polymers in sharp contrast to conventional antibiotics and lipopeptides, thus the polymers hold great promise to be used as coating materials for developing permanent antimicrobial paint.

A Novel Surface Structure Consisting of Contact-active Antibacterial Upper-layer and Antifouling Sub-layer Derived from Gemini Quaternary Ammonium Salt Polyurethanes

“…Moreover, recent researches demonstrate that the positively charged quaternary ammonium salts on the polyurethane film surfaces first interact with the negatively charged phospholipid head groups of the bacteria cytoplasmic membrane, causing general perturbation of the lipid bilayer. The long hydrophobic alkyl chains then pierce the membranes of these surface-attached bacteria, forming holes that cause cytoplasm leakage, lysis, and death4243. Because hydrophilic PEG chains combining with carboxyl anions exhibit a high resistance to protein adsorption2144, the bacterial residues remaining on the film surface are shed and the contact-active antibacterial function restored (Fig.…”

Recent Developments in Antimicrobial Polymers: A Review

“…The cationic polymers interact with the bacterial and fungal cell membrane, disrupting the integrity of the lipid membrane, affecting the transport of compounds across the membranes and, finally, leading to cell death [51]. …”

Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection

“…Further, the membrane-active mode of action of these polymers might target slow or non-dividing as well as antibiotic tolerant bacteria in biofilms resulting in their eradication [11]. Cationic charge of these polymers drive them towards the negatively charged lipid membranes of bacteria and hydrophobicity leads to insertion into cell membranes, thus leading to disruption of membrane integrity and cell death [32][33][34]. Their selective interaction with bacteria results from the fact that mammalian cell (for e.g.…”