Amphiphilic Nano-Swords for Direct Penetration and Eradication of Pathogenic Bacterial Biofilms

Abstract

Bacterial biofilms are major causes of persistent and recurrent infections and implant failures. Biofilms are formable by most clinically important pathogens worldwide, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, causing recalcitrance to standard antibiotic therapy or anti-biofilm strategies due to amphiphilic impermeable extracellular polymeric substances (EPS) and the presence of resistant and persistent bacteria within the biofilm matrix. Herein, we report our design of an oligoamidine-based amphiphilic “nano-sword” with high structural compacity and rigidity. Its rigid, amphiphilic structure ensures effective penetration into EPS, and the membrane-DNA dual-targeting mechanism exerts strong bactericidal effect on the dormant bacterial persisters within biofilms. The potency of this oligoamidine is shown in two distinct modes of application: it may be used as a coating agent for polycaprolactone to fully inhibit surface biofilm growth in an implant-site mimicking micro-environment; meanwhile, it cures model mice of biofilm infections in various ex vivo and in vivo studies.

Broad-Spectrum Antimicrobial Polymer with Dual Bactericidal Mechanisms Enhances Antibiotic Activity in the Treatment of Fish Infections

“…Similar to our previously reported oligomers, ,− P C3–8 also exhibited a dual mechanism of action in killing pathogenic bacteria. We first investigated their binding affinity toward bacterial membranes.…”

Self-Assembled Borneol-Guanidine-Based Amphiphilic Polymers as an Efficient Antibiofilm Agent

“…aureus, which is the main cause of nosocomial infections. , As BGN 2 - n shows excellent bacteriostatic and bactericidal activity against S. aureus, we evaluated its ability to inhibit biofilm formation and ablate mature biofilms using crystal violet staining and CLSM. ,, BGN 2 - n is found to exhibit superior inhibition for S. aureus biofilm formation at low concentrations.…”

“…Bacterial infections with drug-resistant bacteria pose a major challenge in treating the infection, and biofilm formation at the adhesion interface contributes significantly to drug resistance. , About 65% of microbial infections and 80% of chronic infections in humans are biofilms-associated according to the U.S. National Institutes of Health. − A biofilm is a three-dimensional microbial community encapsulated in self-secreted extracellular polymeric substances (EPS) that are composed of polysaccharides, proteins, lipids, and extracellular DNA. ,, Bacteria in biofilms are 10–1000 times more resistant to antibiotics than plankton bacteria. The densely packed EPS prevents the bacteria from being attacked by the host immune system , and restricts the activity of antibacterial agents by limiting drug penetration, enhancing drug efflux and quorum sensing. ,− Recent antibiofilm strategies include disturbing the synthesis of EPS, interfering with metabolic activity, or directly killing persister cells. ,, The use of high-dose antibiotics is commonly recommended for treating biofilm-associated infections caused by bacteria with a low metabolic rate.…”

Recent Advances of Composite Nanomaterials for Antibiofilm Application

“…Xinxin Feng and colleagues [57] constructed an amphiphilic oligamine (3a) with a rigid structure for the direct penetration and eradication of biofilms via oligamine-based peptidomimetic studies (Figure 10A). Among the synthesized aggregates, 3a oligomer had the lowest MIC value (0.25-2 µg•mL −1 ) and MBIC value (16 µg•mL −1 ), and a strong broadspectrum antibacterial activity against S. aureus.…”