title: Highly potent antimicrobial polyionenes with rapid killing kinetics, skin biocompatibility and in vivo bactericidal activity.
abstract: Effective antimicrobial agents are important arsenals in our perennial fight against communicable diseases, hospital-acquired and surgical site multidrug-resistant infections. In this study, we devise a strategy for the development of highly efficacious and skin compatible yet inexpensive water-soluble macromolecular antimicrobial polyionenes by employing a catalyst-free, polyaddition polymerization using commercially available monomers. A series of antimicrobial polyionenes are prepared through a simple polyaddition reaction with both polymer-forming reaction and charge installation occurring simultaneously. The compositions and structures of polymers are modulated to study their effects on antimicrobial activity against a broad spectrum of pathogenic microbes. Polymers with optimized compositions have potent antimicrobial activity with low minimum inhibitory concentrations of 1.95-7.8 μg/mL and high selectivity over mammalian cells. In particular, a killing efficiency of more than 99.9% within 2 min is obtained. Moreover, the polymers demonstrate high antimicrobial efficacy against various clinically-isolated multidrug-resistant microbes, yet exhibit vastly superior skin biocompatibility in mice as compared to other clinically used surgical scrubs (chlorhexidine and betadine). Microbicidal activity of the polymer is mediated via membrane lysis as demonstrated by confocal microscopy. Unlike small molecular antibiotics, repeated use of the polymer does not induce drug resistance. More importantly, the polymer shows excellent bactericidal activity in a P. aeruginosa-contaminated mouse skin model. Given their rapid and efficacious microbicidal activity and skin compatibility, these polymers have tremendous potential to be developed as surgical scrubs/hand sanitizers to prevent multidrug-resistant infections.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Shaoqiong
authors.initials: S
authors.lastname: Liu
authors.affiliation: IBM Almaden Research Center, 650 Harry Rd, San Jose, CA, 95120, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ono
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Jye Yng
authors.initials: JY
authors.lastname: Teo
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Zhen Chang
authors.initials: ZC
authors.lastname: Liang
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, China; First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
authors.forename: Kaijin
authors.initials: K
authors.lastname: Xu
authors.affiliation: IBM Almaden Research Center, 650 Harry Rd, San Jose, CA, 95120, USA.
authors.forename: Musan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
authors.forename: Guansheng
authors.initials: G
authors.lastname: Zhong
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Jeremy P K
authors.initials: JP
authors.lastname: Tan
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ng
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Chuan
authors.initials: C
authors.lastname: Yang
authors.affiliation: IBM Almaden Research Center, 650 Harry Rd, San Jose, CA, 95120, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Chan
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, China; First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
authors.forename: Zhongkang
authors.initials: Z
authors.lastname: Ji
authors.affiliation: First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Bao
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Kiran
authors.initials: K
authors.lastname: Kumar
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Shujun
authors.initials: S
authors.lastname: Gao
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Ashlynn
authors.initials: A
authors.lastname: Lee
authors.affiliation: IBM Almaden Research Center, 650 Harry Rd, San Jose, CA, 95120, USA.
authors.forename: Mareva
authors.initials: M
authors.lastname: Fevre
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, China; First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Jackie Y
authors.initials: JY
authors.lastname: Ying
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, China; First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
authors.forename: Lanjuan
authors.initials: L
authors.lastname: Li
authors.affiliation: First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
authors.affiliation: IBM Almaden Research Center, 650 Harry Rd, San Jose, CA, 95120, USA. Electronic address: hedrick@us.ibm.com.
authors.forename: James L
authors.initials: JL
authors.lastname: Hedrick
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore. Electronic address: yyyang@ibn.a-star.edu.sg.
authors.forename: Yi Yan
authors.initials: YY
authors.lastname: Yang
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology; D002850:Chromatography, Gel; D015169:Colony Count, Microbial; D005260:Female; D005658:Fungi / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D007700:Kinetics; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D008970:Molecular Weight; D011108:Polymers / Q000494:pharmacology*; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000382:microbiology*
chemical_list: D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D011108:Polymers
keywords: Antimicrobial polymers; Broad-spectrum antimicrobial activity; In vivo bactericidal activity; Multidrug-resistant microbes; Polyionenes; Superfast killing kinetics