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Bacterial Biofilm Eradication Agents: A Current Review.

ABSTRACT: Most free-living bacteria can attach to surfaces and aggregate to grow into multicellular communities encased in extracellular polymeric substances called biofilms. Biofilms are recalcitrant to antibiotic therapy and a major cause of persistent and recurrent infections by clinically important pathogens worldwide (e.g., Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus). Currently, most biofilm remediation strategies involve the development of biofilm-inhibition agents, aimed at preventing the early stages of biofilm formation, or biofilm-dispersal agents, aimed at disrupting the biofilm cell community. While both strategies offer some clinical promise, neither represents a direct treatment and eradication strategy for established biofilms. Consequently, the discovery and development of biofilm eradication agents as comprehensive, stand-alone biofilm treatment options has become a fundamental area of research. Here we review our current understanding of biofilm antibiotic tolerance mechanisms and provide an overview of biofilm remediation strategies, focusing primarily on the most promising biofilm eradication agents and approaches. Many of these offer exciting prospects for the future of biofilm therapeutics for a large number of infections that are currently refractory to conventional antibiotics.

SUBMITTER: Verderosa AD

PROVIDER: S-EPMC6893625 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Bacterial Biofilm Eradication Agents: A Current Review.

Verderosa Anthony D AD Totsika Makrina M Fairfull-Smith Kathryn E KE

Frontiers in chemistry 20191128

Most free-living bacteria can attach to surfaces and aggregate to grow into multicellular communities encased in extracellular polymeric substances called biofilms. Biofilms are recalcitrant to antibiotic therapy and a major cause of persistent and recurrent infections by clinically important pathogens worldwide (e.g., <i>Pseudomonas aeruginosa, Escherichia coli</i>, and <i>Staphylococcus aureus</i>). Currently, most biofilm remediation strategies involve the development of biofilm-inhibition ag ...[more]

PMID: 31850313

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Project description:Magnetically driven robots can perform complex functions in biological settings with minimal destruction. However, robots designed to damage deleterious biostructures could also have important impact. In particular, there is an urgent need for new strategies to eradicate bacterial biofilms as we approach a post-antibiotic era. Biofilms are intractable and firmly attached structures ubiquitously associated with drug-resistant infections and destruction of surfaces. Existing treatments are inadequate to both kill and remove bacteria leading to reinfection. Here we design catalytic antimicrobial robots (CARs) that precisely and controllably kill, degrade and remove biofilms with remarkable efficiency. CARs exploit iron oxide nanoparticles (NPs) with dual catalytic-magnetic functionality that (i) generate bactericidal free radicals, (ii) breakdown the biofilm exopolysaccharide (EPS) matrix, and (iii) remove the fragmented biofilm debris via magnetic field driven robotic assemblies. We develop two distinct CAR platforms. The first platform, the biohybrid CAR, is formed from NPs and biofilm degradation products. After catalytic bacterial killing and EPS disruption, magnetic field gradients assemble NPs and the biodegraded products into a plow-like superstructure. When driven with an external magnetic field, the biohybrid CAR completely removes biomass in a controlled manner, preventing biofilm regrowth. Biohybrid CARs can be swept over broad swathes of surface or can be moved over well-defined paths for localized removal with microscale precision. The second platform, the 3D molded CAR, is a polymeric soft robot with embedded catalytic-magnetic NPs, formed in a customized 3D printed mold to perform specific tasks in enclosed domains. Vane-shaped CARs remove biofilms from curved walls of cylindrical tubes, and helicoid-shaped CARs drill through biofilm clogs, while simultaneously killing bacteria. In addition, we demonstrate applications of CARs to target highly confined anatomical surfaces in the interior of human teeth. These 'kill-degrade-and-remove' CARs systems could have significant impact in fighting persistent biofilm-infections and in mitigating biofouling of medical devices and diverse surfaces.

Dataset Information

Bacterial Biofilm Eradication Agents: A Current Review.

Publications

Bacterial Biofilm Eradication Agents: A Current Review.

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