Mechanistic insights into nanoparticle surface-bacterial membrane interactions in overcoming antibiotic resistance

Abstract

Antimicrobial Resistance (AMR) raises a serious concern as it contributes to the global mortality by 5 million deaths per year. The overall impact pertaining to significant membrane changes, through broad spectrum drugs have rendered the bacteria resistant over the years. The economic expenditure due to increasing drug resistance poses a global burden on healthcare community and must be dealt with immediate effect. Nanoparticles (NP) have demonstrated inherent therapeutic potential or can serve as nanocarriers of antibiotics against multidrug resistant (MDR) pathogens. These carriers can mask the antibiotics and help evade the resistance mechanism of the bacteria. The targeted delivery can be fine-tuned through surface functionalization of Nanocarriers using aptamers, antibodies etc. This review covers various molecular mechanisms acquired by resistant bacteria towards membrane modification. Mechanistic insight on ‘NP surface-bacterial membrane’ interactions are crucial in deciding the role of NP as therapeutic. Finally, we highlight the potential accessible membrane targets for designing smart surface-functionalized nanocarriers which can act as bacteria-targeted robots over the existing clinically available antibiotics. As the bacterial strains around us continue to evolve into resistant versions, nanomedicine can offer promising and alternative tools in overcoming AMR.

Ciprofloxacin- and levofloxacin-loaded nanoparticles efficiently suppressed fluoroquinolone resistance and biofilm formation in Acinetobacter baumannii

“…The efflux-resistant mechanism was defeated by F CIP and F LEV , as evidenced by the fact that their MIC was four times lower than that of free CIP and LEV, respectively, on A. baumannii isolates with efflux pump activity. NPs can bypass efflux pumps by acting as a Trojan horse, delivering antimicrobials, or by interacting with efflux pumps to create irreversible blockage 31 , 46 . This notion is strongly supported by the result that MIC for XDR strains without drug efflux pumps was not affected by co-treatment of CCCP with LEV and CIP, either, free or encapsulated into NPs.…”

Green synthesis of silver nanoparticle using pollen extract from Tetragonisca angustula a stingless bee

“…Antimicrobial resistance poses a significant global public health challenge. Recently, silver nanoparticles produced through chemical synthesis have been gaining prominence in research demonstrating their effectiveness against various bacteria resistant to commercial antibiotics [ 50 ]. In this study, our findings demonstrate the efficacy of silver nanoparticles (AgNPs) derived from methanolic extract of pollen against both Escherichia coli mcr and Staphylococcus aureus MRSA.…”

Nanosilver: An Old Antibacterial Agent with Great Promise in the Fight against Antibiotic Resistance

“…AgNPs facilitate ROS release by competing with amino acids (especially cis ) that coordinate Fe-S clusters in complexes of the electron transport chain [ 302 ]. While some ROS may be eliminated by bacteria, large amounts of ROS destabilize the bacterial cell membrane due to lipid peroxidation [ 303 ]. As a result, antibiotics that would otherwise be prevented from entering the cell are allowed to seep through the damaged membrane.…”

“…Evading enzymes that destroy antibiotics : One of the best-known resistance mechanisms is the enzymatic destruction of antibiotics through the action of β-lactamase (against ampicillin) and chloramphenicol acyltransferase. In this scenario, AgNPs carrying antibiotics act as a Trojan-horse delivery vehicle camouflaging their cargo [ 303 ]. Treatment of intracellular bacteria by antibiotic conjugates: Intracellular bacteria are species that produce infection by residing in mammalian cells, as is seen with the bacterial pathogen M. tuberculosis .…”

“…Challenges and future directions : Even though AgNP–antibiotic conjugates have demonstrated potential in treating infections caused by MDR bacteria, there are few U.S. FDA-approved treatments that use AgNP–antibiotic conjugates [ 303 ]. To address this, improvements must be made in batch-to-batch reproducibility of AgNP during synthesis (especially biological), developing dose–response relationships, and advancing the use of organism models (in vitro and in vivo) to bridge the gap between promising potential and the establishment of AgNP–antibiotic conjugates as effective treatments.…”