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.
Highlights
Biofilm formation is a significant virulence mechanism in the pathogenesis of many medically important bacterial pathogens, such as Pseudomonas aeruginosa (Gellatly and Hancock, 2013), Staphylococcus aureus (Gordon and Lowy, 2008), and Escherichia coli (Beloin et al, 2008)
Considering most antibiotics target rapidly replicating bacterial cells, it is of little surprise that areas of slowgrowing or dormant cells within a biofilm would be unaffected by antibiotics and exhibit high levels of antibiotic tolerance
This study clearly demonstrated the use of cephalosporin3′-diazeniumdiolate as a targeted nitric oxide-releasing agent, and more agents have been reported by the same group that significantly reduce a biofilm population, these compounds remain to be tested for biofilm eradication (Yepuri et al, 2013)
Summary
Biofilm formation is a significant virulence mechanism in the pathogenesis of many medically important bacterial pathogens, such as Pseudomonas aeruginosa (Gellatly and Hancock, 2013), Staphylococcus aureus (Gordon and Lowy, 2008), and Escherichia coli (Beloin et al, 2008). One biofilm-related infection of particular medical concern is P. aeruginosa biofilms in the lungs of cystic fibrosis patients This opportunistic pathogen has been known to cause acute and chronic lung infections that can result in significant morbidity and mortality (Wagner and Iglewski, 2008). Microbial adhesion resulting in biofilm formation on implanted medical devices is a common occurrence and can lead to serious illness and death (Habash and Reid, 1999) These implanted medical devices, which can include intravascular catheters, urinary catheters, pacemakers, heart valves, stents, and orthopedic implants, are commonly used to saves lives but can present a significant health risk when colonized by bacterial biofilms (Francolini and Donelli, 2010). This review presents an overview of bacterial biofilm development and the current methods used to prevent, disperse, and treat bacterial biofilms, with a particular focus on the development of novel biofilm eradication strategies
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