Qian Zhou,Kunpeng Li,Kun Wang,Weilin Hong,Jingjie Chen,Jin Chai,Luofeng Yu,Zhangyong Si,Peng Li
ESKAPE pathogens are a panel of most recalcitrant bacteria that could “escape” the treatment of antibiotics and exhibit high incidence of drug resistance. The emergence of multidrug-resistant (MDR) ESKAPE pathogens (particularly Gram-negative bacteria) accounts for high risk of mortality and increased resource utilization in health care. Worse still, there has been no new class of antibiotics approved for exterminating the Gram-negative bacteria for more than 50 years. Therefore, it is urgent to develop novel antibacterial agents with low resistance and potent killing efficacy against Gram-negative ESKAPE pathogens. Herein, we present a class of fluoropolymers by mimicking the amphiphilicity of cationic antimicrobial peptides. Our optimal fluoroamphiphilic polymer (PD45HF5) displayed selective antimicrobial ability for all MDR Gram-negative ESAKPE pathogens, low resistance, high in vitro cell selectivity, and in vivo curative efficacy. These findings implied great potential of fluoroamphiphilic cationic polymers as promising antibacterial agents against MDR Gram-negative ESKAPE bacteria and alleviating antibiotic resistance.
Sidi Liu,Guimei Jiang,Rui Shi,Renfei Wu,Xiang Xiao,Tianrong Yu,Yijin Ren,Henny C. van der Mei,Henk J. Busscher,Jian Liu
Extracorporeal devices to cleanse blood from infecting bacteria are based upon bacterial capture to surfaces, but the current generation of capture devices has variable and inconclusive therapeutic efficacy. Here, a microfluidic device equipped with a Si capture surface with a highly periodic nanowired structure is designed. Nanowired Si surfaces are coated with macrophage membranes to benefit from the natural blood compatibility and ligand–receptor binding of macrophages. When macrophages are activated by uptake of Staphylococcus aureus or Escherichia coli , zeta potentials of activated macrophage membrane coatings become less negative than those of nonactivated ones, stimulating nonspecific bacterial capture. In addition, Toll-like receptors in bacterially activated membrane coatings on nanowired surfaces that are absent in nonactivated membrane coatings contribute to specific bacterial capture. These two factors, together with the maintenance of fluidity in activated membrane coatings, cause broad spectrum, high capture efficiencies of all six ESKAPE member pathogens, considered most threatening to human health. Surfaces with such broad-spectrum capture efficiencies have not been previously described, but are clinically most relevant because blood cleansing should start as soon as possible after a septic patient becomes symptomatic, when the causative bacterial strain is still unknown.
Infections caused by Enterococcus fascism, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) bacteria and their biofilms considerably threaten human health. Developing antibacterial agents against ESKAPE bacteria and controlling related inflammation are urgently needed. Herein, we developed a nanosystem by coating M1 macrophage membranes onto the surface of Prussian Blue@polydopamine@IR820 nanoparticles (PDIM NPs) for determining the antimicrobial activity against skin and soft tissue infection. Upon administration, PDIM NPs actively aggregated in the infected regions of subcutaneous abscesses owing to their homologous targeting properties. Under irradiation with a near-infrared (NIR) 808 nm laser, PDIM NPs exhibited outstanding antibacterial effects via synergistic photothermal and photodynamic therapy. Thereafter, the naked Prussian Blue-based nanoparticles effectively scavenged excessive reactive oxygen species and alleviated inflammation. The mouse model demonstrated the regulation of angiogenesis, collagen deposition, and attenuated hyperinflammation. Furthermore, PDIM NPs exhibited excellent biosafety in vitro and in vivo. Therefore, PDIM NPs showed remarkable infectious site-targeting properties and antimicrobial performances and facilitated the healing of cutaneous abscesses, providing strategies for treating ESKAPE bacteria and biofilm-associated diseases.
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