A new surface charge neutralizing nano-adjuvant to potentiate polymyxins in killing Mcr-1 mediated drug-resistant Escherichia coli

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Title
A new surface charge neutralizing nano-adjuvant to potentiate polymyxins in killing Mcr-1 mediated drug-resistant Escherichia coli
Author(s)
H Cho; A Naskar; S LeeSemi Kim; K S Kim
Bibliographic Citation
Pharmaceutics, vol. 13, no. 2, pp. 250-250
Publication Year
2021
Abstract
Resistance to polymyxins when treating multidrug-resistant (MDR) Gram-negative bacterial infections limit therapeutic options. Here, we report the synthesis of a nickel (Ni) doped Zinc oxide (NZO) combined with black phosphorus (BP) (NZB) nanocomposite and its synergistic action with polymyxin B (PolB) against polymyxin-resistant Escherichia coli harboring mobilized colistin resistance (mcr-1) gene. NZB and PolB combination therapy expressed a specific and strong synergy against Mcr-1 expressing E. coli cells. The underlying mechanism of the synergy is the charge neutralization of the E. coli cell surface by NZB, resulting in a more feasible incorporation of PolB to E. coli. The synergistic concentration of NZB with PolB was proved biocompatible. Thus, the NZB is the first biocompatible nano-adjuvant to polymyxins against polymyxin-resistant E. coli cells, recognizing the physical status of bacteria instead of known adjuvants targeting cellular gene products. Therefore, NZB has the potential to revive polymyxins as leading last-resort antibiotics to combat polymyxin-resistant Gram-negative bacterial infections.
Keyword
Nano-antibioticsBlack phosphorusPolymyxin-resistant Gram-negative bacteriaCharge neutralization mechanismMcr-1
ISSN
1999-4923
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/pharmaceutics13020250
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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