Immobilized N-alkylated polyethylenimine avidly kills bacteria by rupturing cell membranes with no resistance developed.

Several critical mechanistic and phenomenological aspects of the microbicidal surface coatings based on immobilized hydrophobic polycations, previously developed by us, are addressed. Using Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria, remarkable bactericidal action (up to a 10(9)-fold reduction in live bacteria count in the surface-exposed solution and a 100% inactivation of the surface-adhered bacteria) of an amino-glass slide covalently derivatized with N-hexyl,methyl-polyethylenimine (PEI) is found to be due to rupturing bacterial cell membranes by the polymeric chains. The bacteria fail to develop noticeable resistance to this lethal action over the course of many successive generations. Finally, the immobilized N-alkyl-PEI, while deadly to bacteria, is determined to be harmless to mammalian (monkey kidney) cells.

[1]  R. Koepsel,et al.  Permanent, nonleaching antibacterial surfaces. 1. Synthesis by atom transfer radical polymerization. , 2004, Biomacromolecules.

[2]  D. M. Lynn,et al.  Biocidal activity of polystyrenes that are cationic by virtue of protonation. , 2004, Organic letters.

[3]  Jin‐San Yoon,et al.  Antimicrobial activity of a monomer and its polymer based on quinolone , 2003 .

[4]  Koon Gee Neoh,et al.  Surface Functionalization Technique for Conferring Antibacterial Properties to Polymeric and Cellulosic Surfaces , 2003 .

[5]  A. Klibanov,et al.  Making thin polymeric materials, including fabrics, microbicidal and also water-repellent , 2003, Biotechnology Letters.

[6]  A. Klibanov,et al.  Mechanism of bactericidal and fungicidal activities of textiles covalently modified with alkylated polyethylenimine. , 2003, Biotechnology and bioengineering.

[7]  J. Maillard,et al.  Aspects of the antimicrobial mechanisms of action of a polyquaternium and an amidoamine. , 2003, The Journal of antimicrobial chemotherapy.

[8]  K. Melkonian,et al.  Preparation and investigation of antibacterial carbohydrate-based surfaces. , 2002, Carbohydrate research.

[9]  A. Klibanov,et al.  Enhancing polyethylenimine's delivery of plasmid DNA into mammalian cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Sang Beom Lee,et al.  Polymer surfaces derivatized with poly(vinyl-N-hexylpyridinium) kill airborne and waterborne bacteria. , 2002, Biotechnology and bioengineering.

[11]  Sang Beom Lee,et al.  Insights into bactericidal action of surface-attached poly(vinyl-N-hexylpyridinium) chains , 2002, Biotechnology Letters.

[12]  R. J. Doerksen,et al.  De novo design of biomimetic antimicrobial polymers , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M. Edge,et al.  The enhanced performance of biocidal additives in paints and coatings , 2001 .

[14]  S. Cooper,et al.  Synthesis and characterization of non-leaching biocidal polyurethanes. , 2001, Biomaterials.

[15]  Alexander M. Klibanov,et al.  Designing surfaces that kill bacteria on contact , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  K. Lewis,et al.  Riddle of Biofilm Resistance , 2001, Antimicrobial Agents and Chemotherapy.

[17]  D. König,et al.  Novel Strategies to Prevent Catheter-Associated Infections in Oncology Patients , 2001, Journal of chemotherapy.

[18]  S. Cooper,et al.  Recent Advances in Antimicrobial Dendrimers , 2000 .

[19]  A. D. Russell,et al.  Bacterial resistance to disinfectants: present knowledge and future problems. , 1999, The Journal of hospital infection.

[20]  C. Alexander,et al.  Bacterial Adhesion at Synthetic Surfaces , 1999, Applied and Environmental Microbiology.

[21]  J. Costerton,et al.  Bacterial biofilms: a common cause of persistent infections. , 1999, Science.

[22]  A. D. Russell,et al.  Antiseptics and Disinfectants: Activity, Action, and Resistance , 1999, Clinical Microbiology Reviews.

[23]  M. Torii,et al.  Antibacterial activity of dentine primer containing MDPB after curing. , 1998, Journal of dentistry.

[24]  T. Nonaka,et al.  Antibacterial activity of resin-containing triethylenetetramine side chains and/or thiol groups-metal complexes , 1996 .

[25]  L. Evans,et al.  Further studies investigating a potential non‐leaching biocide using the marine fouling diatom Amphora coffeaeformis , 1995 .

[26]  J. McCabe,et al.  Antibacterial activity of MDPB polymer incorporated in dental resin. , 1995, Journal of dentistry.

[27]  M. Vaara,et al.  Agents that increase the permeability of the outer membrane. , 1992, Microbiological reviews.

[28]  Hilary M. Lappin-Scott,et al.  Bacterial biofilms and surface fouling , 1989 .

[29]  M. Nishiguchi,et al.  Antibacterial activity of soluble pyridinium-type polymers , 1988, Applied and environmental microbiology.

[30]  R. Colwell,et al.  Survival strategies of bacteria in the natural environment. , 1987, Microbiological reviews.

[31]  D.R. Battice,et al.  A New Technology for Producing Stabilized Foams Having Antimicrobial Activity , 1985 .

[32]  T. Ikeda,et al.  New polymeric biocides: synthesis and antibacterial activities of polycations with pendant biguanide groups , 1984, Antimicrobial Agents and Chemotherapy.

[33]  J. Frame.  Porous calcium sulphate dihydrate as a biodegradable implant in bone. , 1975, Journal of dentistry.

[34]  A. Isquith,et al.  Surface-bonded antimicrobial activity of an organosilicon quaternary ammonium chloride. , 1972, Applied microbiology.

[35]  S. Levy.  The antibiotic paradox : how the misuse of antibiotics destroys their curative powers , 2002 .

[36]  A. Klibanov,et al.  Bactericidal Properties of Flat Surfaces and Nanoparticles Derivatized with Alkylated Polyethylenimines , 2002, Biotechnology progress.

[37]  R. Hancock,et al.  Interaction of cationic peptides with bacterial membranes. , 1997, Methods in molecular biology.

[38]  Richard P. Haugland,et al.  Handbook of fluorescent probes and research chemicals , 1996 .

[39]  P. Ferruti,et al.  A comparison between the hemolytic and antibacterial activities of new quaternary ammonium polymers. , 1994, Journal of biomaterials science. Polymer edition.

[40]  J. Macdonald,et al.  New biomaterials through surface segregation phenomenon: new quaternary ammonium compounds as antibacterial agents. , 1994, Journal of biomaterials science. Polymer edition.

[41]  C. R. Arciola,et al.  Heparin surface treatment of poly(methylmethacrylate) alters adhesion of a Staphylococcus aureus strain: utility of bacterial fatty acid analysis. , 1993, Biomaterials.

[42]  S. Denyer.  Mechanisms of action of biocides , 1990 .

[43]  A. D. Russell,et al.  Understanding antibacterial action and resistance , 1990 .