A New Surface Charge Neutralizing Nano-Adjuvant to Potentiate Polymyxins in Killing Mcr-1 Mediated Drug-Resistant Escherichia coli.

Hyejin Cho,Sohee Lee,Semi Kim,Kwang-Sun Kim,Atanu Naskar

doi:10.3390/pharmaceutics13020250

Hyejin Cho, Sohee Lee + Show 3 more

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https://doi.org/10.3390/pharmaceutics13020250

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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.

Highlights

Infections caused by multidrug-resistant (MDR) Gram-negative bacteria pose a serious global mortality burden and an increased death rate
X-ray diffraction (XRD) reflection peaks of the as-synthesized ZO, Ni doped ZnO (NZO), and Ni Doped ZnO-BP (NZB) were consistent with the hexagonal ZO (h-ZO) structure (JCPDS 36-1451) [17]
The charge of nanocomposite was analyzed by the zeta potential

Summary

Introduction

Infections caused by multidrug-resistant (MDR) Gram-negative bacteria pose a serious global mortality burden and an increased death rate. Gram-negative bacteria cause infections including pneumonia, bloodstream infections, wound or surgical site infections, and meningitis [1]. The rapid resistance of Gram-negative bacteria to currently available antibiotics and their innate ability to survive environmental pressure is of great concern. The lack of effective antimicrobial agents to combat MDR pathogens has led to the resurgence of last-resort antibiotics including polymyxins (polymyxin B and colistin) to control MDR Gram-negative bacterial infections [3]. Researchers are trying in different ways such as detection of bacteria which can be utilized to kill bacterial cells [4,5,6]

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