Scientific research is increasingly focused on methods to combat microbial infections resistant to conventional treatments. Many of these infections are caused by microbes living in structured communities, which has led to the exploration of antibiofilm strategies. Understanding these strategies requires knowing what biofilms are and the problems they present.
What Are Biofilms?
Contrary to the perception of microbes as individual, free-floating organisms (a planktonic state), they often gather on surfaces to form structured communities known as biofilms. These can be found almost anywhere with moisture and nutrients, with familiar examples including dental plaque, the slime that clogs drains, and the slippery coating on rocks in a stream. Biofilms can form on natural materials, plastics, metals, and medical implants.
Biofilm formation begins when planktonic microbes attach to a surface. They then produce a slimy, glue-like substance called the extracellular polymeric substance (EPS) matrix. Composed of sugars, proteins, and nucleic acids, this matrix encases the microbial community. This allows it to develop a complex, three-dimensional structure.
A mature biofilm can grow from a few cell layers to several inches thick and often consists of a diverse mix of bacteria, fungi, and other microorganisms. For instance, dental plaque can contain over 500 different bacterial species. The final stage of the life cycle is dispersion, where cells detach to colonize new surfaces and start the cycle again.
Why Biofilms Are a Concern
Biofilms are a significant issue because they provide a protected mode of growth for microorganisms, making them difficult to eliminate. Bacteria within a biofilm can be up to 1,000 times more resistant to antibiotics than their planktonic counterparts. This resistance is why biofilm-related infections are often chronic and recurring, with estimates suggesting they are associated with 65% to 80% of all chronic infections.
The protective nature of the biofilm is due to several factors. The dense EPS matrix acts as a physical barrier that can hinder the penetration of antimicrobial agents. The microorganisms within the biofilm also exhibit different physiological properties than their free-floating counterparts. For example, some bacteria may enter a slower-growing or dormant state, making them less susceptible to antibiotics that target actively dividing cells.
In medical settings, biofilms can form on devices like catheters, artificial joints, and heart valves, creating reservoirs for pathogenic microbes. This increases the risk of hard-to-treat, healthcare-associated infections. Beyond medicine, biofilms cause economic impacts through biofouling and corrosion in industrial equipment, water systems, and on ship hulls.
The Concept of Antibiofilm Strategies
Antibiofilm strategies are methods developed to either prevent the formation of biofilms or eradicate them once formed. This represents a new paradigm in treating infections, moving beyond conventional antibiotics that are often ineffective against these communities.
The goals of antibiofilm strategies are twofold: prevention and eradication. Prevention involves interfering with the initial stages of biofilm development to stop them from forming. Eradication focuses on breaking down and eliminating mature biofilms, a departure from traditional antibiotic discovery that tested drugs against planktonic bacteria.
Unlike standard antibiotics, antibiofilm agents are designed to overcome the unique defenses of biofilm communities. This can involve weakening the biofilm structure to make the embedded bacteria more vulnerable or using agents that can kill the protected cells.
How Antibiofilm Strategies Work
Antibiofilm strategies use various mechanisms to prevent or disrupt biofilms by targeting different stages of their life cycle. These approaches can be categorized as those that prevent biofilm formation and those that target existing biofilms.
One approach to prevention is interfering with the initial attachment of microbes to a surface. This can be done by applying coatings that make it difficult for bacteria to adhere. Another tactic is blocking quorum sensing, the cell-to-cell communication bacteria use to coordinate activities. Molecules called quorum-sensing inhibitors disrupt these signals, preventing the effort required to build a biofilm.
To combat established biofilms, one strategy is to break down the protective EPS matrix. This can be accomplished using enzymes that degrade matrix components like polysaccharides and DNA, which exposes the embedded bacteria and makes them more susceptible to antimicrobial agents. Other strategies focus on killing the resilient “persister” cells within the biofilm that can survive antibiotic treatment.
This can involve using novel molecules that penetrate the biofilm to kill these less active cells. Bacteriophages, which are viruses that infect bacteria, are also being explored to specifically target and eliminate bacteria within biofilms. Combining these antibiofilm agents with traditional antibiotics is another promising approach to enhance treatment efficacy.