title: 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.
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bangalore 560064, India.
authors.forename: Jiaul
authors.initials: J
authors.lastname: Hoque
authors.forename: Padma
authors.initials: P
authors.lastname: Akkapeddi
authors.forename: Vikas
authors.initials: V
authors.lastname: Yadav
authors.forename: Goutham B
authors.initials: GB
authors.lastname: Manjunath
authors.forename: Divakara S S M
authors.initials: DS
authors.lastname: Uppu
authors.forename: Mohini M
authors.initials: MM
authors.lastname: Konai
authors.forename: Venkateswarlu
authors.initials: V
authors.lastname: Yarlagadda
authors.forename: Kaustuv
authors.initials: K
authors.lastname: Sanyal
authors.forename: Jayanta
authors.initials: J
authors.lastname: Haldar
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects*; D003428:Cross Infection / Q000382:microbiology; D006801:Humans; D010150:Paint / Q000032:analysis* / Q000382:microbiology; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D011108:Polymers
keywords: antibacterial activity; antifungal activity; bacterial resistance; contact-based noncovalent antimicrobial coating; membrane-active mode of action; microbicidal paint; water-insoluble and organo-soluble polymers