Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/138782
Title: A glycosylated cationic block poly (β‐peptide) reverses intrinsic antibiotic resistance in all ESKAPE Gram‐negative bacteria
Authors: Si, Zhangyong
Lim, Hui Wen
Tay, Moon Yue Feng
Du, Yu
Ruan, Lin
Qiu, Haofeng
Zamudio-Vazquez, Rubí
Reghu, Sheethal
Chen, Yahua
Tiong, Wen Shuo
Marimuthu, Kalisvar
De, Partha Pratim
Ng, Oon Tek
Zhu, Yabin
Gan, Yunn-Hwen
Chi, Robin Yonggui
Duan, Hongwei
Bazan, Guillermo C.
Greenberg, E. Peter
Chan-Park, Mary Bee Eng
Pethe, Kevin
Keywords: Engineering::Bioengineering
Issue Date: 2020
Source: Si, Z., Lim, H. W., Tay, M. Y. F., Du, Y., Ruan, L., Qiu, H., . . . K, P. (2020). A glycosylated cationic block poly (β‐peptide) reverses intrinsic antibiotic resistance in all ESKAPE Gram‐negative bacteria. Angewandte Chemie International Edition, 59(17), 6819-6826. doi:10.1002/anie.201914304
Journal: Angewandte Chemie International Edition
Abstract: Carbapenem‐resistant Gram‐negative bacteria (GNB) are heading the list of pathogens for which antibiotics are the most critically needed. Many antibiotics are either unable to penetrate the outer‐membrane or are excluded by efflux mechanisms. Here, we report a cationic block β‐peptide (PAS8‐b‐PDM12) that reverses intrinsic antibiotic resistance in GNB by two distinct mechanisms of action. PAS8‐b‐PDM12 does not only compromise the integrity of the bacterial outer‐membrane, it also deactivates efflux pump systems by dissipating the transmembrane electrochemical potential. As a result, PAS8‐b‐PDM12 sensitizes carbapenem‐ and colistin‐resistant GNB to multiple antibiotics in vitro and in vivo. The β‐peptide allows the perfect alternation of cationic versus hydrophobic side chains, representing a significant improvement over previous antimicrobial α‐peptides sensitizing agents. Together, our results indicate that it is technically possible for a single adjuvant to reverse innate antibiotic resistance in all pathogenic GNB of the ESKAPE group, including those resistant to last resort antibiotics.
URI: https://hdl.handle.net/10356/138782
ISSN: 1433-7851
DOI: 10.1002/anie.201914304
Rights: This is the peer reviewed version of the following article: Si, Z., Lim, H. W., Tay, M. Y. F., Du, Y., Ruan, L., Qiu, H., . . . K, P. (2020). A glycosylated cationic block poly (β‐peptide) reverses intrinsic antibiotic resistance in all ESKAPE Gram‐negative bacteria. Angewandte Chemie International Edition, 59(17), 6819-6826, which has been published in final form at http://doi.org/10.1002/anie.201914304. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCBE Journal Articles

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