TY - JOUR
T1 - Antibacterial low molecular weight cationic polymers
T2 - Dissecting the contribution of hydrophobicity, chain length and charge to activity
AU - Grace, James Lynden
AU - Huang, Johnny X
AU - Cheah, S.-E.
AU - Truong Phuoc, Nghia
AU - Cooper, Matthew A
AU - Li, Jian
AU - Davis, T.P.
AU - Quinn, J.F.
AU - Velkov, T.
AU - Whittaker, M.R.
N1 - Export Date: 25 July 2016
CODEN: RSCAC
Correspondence Address: Whittaker, M.R.; Australian Research Council, Centre of Excellence in Convergent Bio-Nano Science and Technology, 381 Royal Pde, Australia; email: [email protected]
References: (2014) CDC-Get Smart: Know When Antibiotics Work 2013, , http://www.cdc.gov/getsmart/antibiotic-use/antibiotic-resistance-faqs.html#how-bacteria-resist, 17 April; Nolte, O., (2014) Protein Pept. Lett., 21, pp. 330-335; Rice, L.B., Challenges in identifying new antimicrobial agents effective for treating infections with Acinetobacter baumannii and Pseudomonas aeruginosa (2006) Clin. Infect. Dis., 43, pp. S100-S105; Chambers, H.F., (2001) Postgrad. Med., 109, pp. 43-50; Who, (2014) ANTIMICROBIAL RESISTANCE Global Report on Surveillance, , WHO Library; Ling, L.L., Schneider, T., Peoples, A.J., Spoering, A.L., Engels, I., Conlon, B.P., (2015) Nature, 517, pp. 455-459; Yeung, A.T.Y., Gellatly, S.L., Hancock, R.E.W., (2011) Cell. Mol. Life Sci., 68, pp. 2161-2176; Nederberg, F., Zhang, Y., Tan, J.P., Xu, K., Wang, H., Yang, C., (2011) Nat. Chem., 3, pp. 409-414; Locock, K.E.S., Michl, T.D., Valentin, J.D.P., Vasilev, K., Hayball, J.D., Qu, Y., (2013) Biomacromolecules, 14, pp. 4021-4031; Giuliani, A., Pirri, G., Nicoletto, S.F., (2007) Cent. Eur. J. Biol., 2, pp. 1-33; Kuroda, K., Caputo, G.A., (2013) Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol., 5, pp. 49-66; Kenawy, E.R., Worley, S.D., Broughton, R., (2007) Biomacromolecules, 8, pp. 1359-1384; Timofeeva, L., Kleshcheva, N., (2011) Appl. Microbiol. Biotechnol., 89, pp. 475-492; Mowery, B.P., Lindner, A.H., Weisblum, B., Stahl, S.S., Gellman, S.H., (2009) J. Am. Chem. Soc., 131, pp. 9735-9745; Michl, T.D., Locock, K.E.S., Stevens, N.E., Hayball, J.D., Vasilev, K., Postma, A., (2014) Polym. Chem., 5, pp. 5813-5822; Gody, G., Maschmeyer, T., Zetterlund, P.B., Perrier, S., (2013) Nat. Commun., 4, pp. 1-9; Anastasaki, A., Nikolaou, V., Nurumbetov, G., Wilson, P., Kempe, K., Quinn, J.F., Davis, T.P., Haddleton, D.M., (2015) Chem. Rev.; Boyer, C., Zetterlund, P.B., Whittaker, M.R., (2014) J. Polym. Sci., Part A: Polym. Chem., 52, pp. 2083-2098; Boyer, C., Soeriyadi, A.H., Zetterlund, P.B., Whittaker, M.R., (2011) Macromolecules, 44, pp. 8028-8033; Soeriyadi, A.H., Boyer, C., Nyström, F., Zetterlund, P.B., Whittaker, M.R., (2011) J. Am. Chem. Soc., 133, pp. 11128-11131; Lee, J., (2007), PhD thesis, University of North CarolinaMartin, T.P., (2007), PhD thesis, Massachusetts Institute of TechnologyRawlinson, L.A.B., Ryan, S.M., Mantovani, G., Syrett, J.A., Haddleton, D.M., Brayden, D.J., (2010) Biomacromolecules, 11, pp. 443-453; Zuo, H.J., Wu, D.C., Fu, R.W., (2010) Polym. J., 42, pp. 766-771; Lin, S., Wu, J.H., Jia, H.Q., Hao, L.M., Wang, R.Z., Qi, J.C., (2013) RSC Adv., 3, pp. 20758-20764; Dutta, P., Dey, J., Shome, A., Das, P.K., (2011) Int. J. Pharm., 414, pp. 298-311; Talbot, G.H., Bradley, J., Edwards, J.E., Gilbert, D., Scheld, M., Bartlett, J.G., (2006) Clin. Infect. Dis., 42, pp. 657-668; Boucher, H.W., Talbot, G.H., Bradley, J.S., Edwards, J.E., Gilbert, D., Rice, L.B., (2009) Clin. Infect. Dis., 48, pp. 1-12; Ciampolini, M., Nardi, N., (1966) Inorg. Chem., 5, pp. 41-44; Anderson, R.C., Hancock, R.E.W., Yu, P.L., (2004) Antimicrob. Agents Chemother., 48, pp. 673-676; Helander, I.M., Mattila-Sandholm, T., (2000) J. Appl. Microbiol., 88, pp. 213-219; Dathe, M., Wieprecht, T., (1999) Biochim. Biophys. Acta, Biomembr., 1462, pp. 71-87; Bütün, V., Armes, S.P., Billingham, N.C., (2001) Macromolecules, 34, pp. 1148-1159; Lu, G., Wu, D., Fu, R., (2007) React. Funct. Polym., 67, pp. 355-366; Tashiro, T., (2001) Macromol. Mater. Eng., 286, pp. 63-87; Li, J., Nation, R.L., Owen, R.J., Wong, S., Spelman, D., Franklin, C., (2007) Clin. Infect. Dis., 45, pp. 594-598; Nikaido, H., (2003) Microbiol. Mol. Biol. Rev., 67, pp. 593-656; Moffatt, J.H., Harper, M., Harrison, P., Hale, J.D.F., Vinogradov, E., Seemann, T., (2010) Antimicrob. Agents Chemother., 54, pp. 4971-4977; Zhang, L.J., Dhillon, P., Yan, H., Farmer, S., Hancock, R.E.W., (2000) Antimicrob. Agents Chemother., 44, pp. 3317-3321; Wang, Y., Zhou, Z., Zhu, J., Tang, Y., Canady, T.D., Chi, E.Y., (2011) Polymers, 3, pp. 1199-1214; Helander, I.M., Nurmiaho-Lassila, E.L., Ahvenainen, R., Rhoades, J., Roller, S., (2001) Int. J. Food Microbiol., 71, pp. 235-244; Johnson, L., Mulcahy, H., Kanevets, U., Shi, Y., Lewenza, S., (2012) J. Bacteriol., 194, pp. 813-826; Rubén, D.L., Tejero, D.L., López-Fabal, F., Gómez-Garcés, J.L., Fernández-García, M., (2015) Polym. Chem., 6, pp. 3449-3459; Punia, A., Mancuso, A., Banerjee, P., Yang, N.-L., (2015) ACS Macro Lett., 4, pp. 426-430; Palermo, E.F., Kuroda, K., (2010) Appl. Microbiol. Biotechnol., 87, pp. 1605-1615; Hwang, T.L., Aljuffali, I.A., Lin, C.F., Chang, Y.T., Fang, J.Y., (2015) Int. J. Nanomed., 10, pp. 371-385; Fischer, D., Li, Y.X., Ahlemeyer, B., Krieglstein, J., Kissel, T., (2003) Biomaterials, 24, pp. 1121-1131; Truong, N.P., Jia, Z.F., Burges, M., McMillan, N.A.J., Monteiro, M.J., (2011) Biomacromolecules, 12, pp. 1876-1882; Lv, H.T., Zhang, S.B., Wang, B., Cui, S.H., Yan, J., (2006) J. Controlled Release, 114, pp. 100-109; Shannahan, J.H., Lai, X.Y., Ke, P.C., Podila, R., Brown, J.M., Witzmann, F.A., (2013) PLoS One, 8, p. 10; Wang, F.J., Yu, L., Monopoli, M.P., Sandin, P., Mahon, E., Salvati, A., (2013) Nanomedicine, 9, pp. 1159-1168; Ilic, N., Novkovic, M., Guida, F., Xhindoli, D., Benincasa, M., Tossi, A., (2013) Biochim. Biophys. Acta, Biomembr., 1828, pp. 1004-1012; Li, Y.M., Bionda, N., Yongye, A., Geer, P., Stawikowski, M., Cudic, P., (2013) ChemMedChem, 8, pp. 1865-1872
PY - 2016
Y1 - 2016
N2 - The balance of cationicity and hydrophobicity can profoundly affect the performance of antimicrobial polymers. To this end a library of 24 cationic polymers with uniquely low degrees of polymerization was synthesized via Cu(0)-mediated polymerization, using three different cationic monomers and two initiators: providing two different hydrocarbon chain tail lengths (C2 and C12). The polymers exhibited structure-dependent antibacterial activity when tested against a selection of bacteria, viz., Staphylococcus aureus ATCC 29213, Klebsiella pneumoniae ATCC 13883, Acinetobacter baumannii ATCC 19606, and Pseudomonas aeruginosa ATCC 27853 as a representative palette of Gram-positive and Gram-negative ESKAPE pathogens. The five best-performing polymers were identified for additional testing against the polymyxin-resistant A. baumannii ATCC 19606R strain. Polymers having the lowest DP and a C12 hydrophobic tail were shown to provide the broadest antimicrobial activity against the bacteria panel studied as evidenced by lower minimum inhibitory concentrations (MICs). An optimal polymer composition was identified, and its mechanism of action investigated via membrane permeability testing against Escherichia coli. Membrane disruption was identified as the most probable mechanism for bacteria cell killing.
AB - The balance of cationicity and hydrophobicity can profoundly affect the performance of antimicrobial polymers. To this end a library of 24 cationic polymers with uniquely low degrees of polymerization was synthesized via Cu(0)-mediated polymerization, using three different cationic monomers and two initiators: providing two different hydrocarbon chain tail lengths (C2 and C12). The polymers exhibited structure-dependent antibacterial activity when tested against a selection of bacteria, viz., Staphylococcus aureus ATCC 29213, Klebsiella pneumoniae ATCC 13883, Acinetobacter baumannii ATCC 19606, and Pseudomonas aeruginosa ATCC 27853 as a representative palette of Gram-positive and Gram-negative ESKAPE pathogens. The five best-performing polymers were identified for additional testing against the polymyxin-resistant A. baumannii ATCC 19606R strain. Polymers having the lowest DP and a C12 hydrophobic tail were shown to provide the broadest antimicrobial activity against the bacteria panel studied as evidenced by lower minimum inhibitory concentrations (MICs). An optimal polymer composition was identified, and its mechanism of action investigated via membrane permeability testing against Escherichia coli. Membrane disruption was identified as the most probable mechanism for bacteria cell killing.
UR - http://www.scopus.com/inward/record.url?scp=84958268074&partnerID=8YFLogxK
U2 - 10.1039/c5ra24361k
DO - 10.1039/c5ra24361k
M3 - Article
AN - SCOPUS:84958268074
SN - 2046-2069
VL - 6
SP - 15469
EP - 15477
JO - RSC Advances
JF - RSC Advances
IS - 19
ER -