Rise to the biofilm challenge: harmful microbes present opportunities for innovators

Traditional antibiotics are growing impotent against biofilms that cause medical infections and product contamination. What can companies do to improve the quality and safety of medicine, agriculture and everyday life, and save billions of dollars in healthcare and contamination costs?

Bacteria or fungi tend to grow as dense communities – biofilms – and become strongly attached to contact surfaces. They are ubiquitous and can cause problems ranging from expensive healthcare-associated infections to industrial contamination.

Biofilms supply protection, food and nutrients to the organisms they host. Depending on the microbial species or where they grow – whether in environmental, biomedical or industrial settings – biofilms can be either beneficial or detrimental. Some, including pathogens or harmful microbes, pose a significant threat to a variety of fields, including healthcare, food processing, household and industrial cleaning, and air and water handling systems. For instance, dental plaque, foggy contact lenses, infected medical implants and sticky fruit surfaces are all consequences of biofilms and cost billions of dollars every year globally in product contamination and medical infections.

The economic damage is huge

Biofilms are difficult to remove, which means they’re a serious risk in agriculture. Plant diseases caused by microbial biofilms contribute to a loss of an estimated 10 per cent of global food supply while foodborne illnesses associated with fresh fruits and vegetables increased dramatically over the 30 years from 1973 to 2003. Biofilms also lead to livestock infections such as bovine mastitis, which was estimated in 2016 to cost the US dairy industry about $2 billion dollars, 11 per cent of the country’s total milk production.

Biofilms have significant human health implications, ranging from dental caries, infected implants and endocarditis to cystic fibrosis. And they account for over 65 per cent of microbial and 80 per cent of chronic infections in the body. Dental caries, a consequence of plaque biofilm, has severe consequences in terms of cost and health but is largely preventable globally.

Tooth decay due to caries affects 25 per cent of all toddlers and 50 per cent of all teenagers in the US. In 2010, the US spent an estimated $105 billion on dental care and services, according to theCenter for Medicare and Medicaid in 2011.

Potentially deadly biofilms cause an estimated 1.7 million hospital acquired infections (HAIs) every year in the US, costing hospitals about $11.5 billion in treatment. HAIs such as surgical site infections, nosocomial diarrhoea, catheter-associated urinary tract infections and central line associated bloodstream infections are a significant cause of patient morbidity and mortality.

Antiseptics and antibiotics are becoming increasingly ineffective against biofilms and often contribute to, rather than combat, antimicrobial resistance.

Resistance fighters: we need new approaches now

In a variety of industries, standard commercial infection control strategies – including antiseptics like bleach, ethanol and biocides, and antibiotics like ampicillin, penicillin and gentamicin – are optimal for targeting free-living, planktonic forms of bacteria.

Biofilms, in contrast, are more difficult to eradicate with conventional antimicrobial agents because their architecture prevents the penetration of these agents and protects the individual organisms within them.

Further, the biofilm colonies may develop and exchange several resistance mechanisms that make them between 20 and 1,000 times less sensitive to biocides and antiseptics than free-living planktonic forms. There is now a growing concern in both academic and industrial communities that the overuse of antibiotics and antiseptics may foster multidrug resistance.

For these reasons, we need new or alternative approaches to address microbial contamination that will prevent, disrupt or treat biofilm formation and growth. Such technologies have the potential to be very specific, highly effective, environmentally safe and not promote resistance.

Prevention, disruption and treatment of biofilm contaminations present a huge underexploited business opportunity.

Time for novel technological solutions

There are 12 overarching intervention points – bacterial and ecological factors – we can use to control biofilms. But not all are equally relevant to every situation.

To control, prevent or change complex biofilm activity and behaviour, we need a multi-disciplinary understanding of the mechanisms of attachment, growth and development, and a broad search strategy to find novel technological solutions.

We need to build a deep knowledge of biofilms in the context of specific environments, relevant organisms and regulatory constraints by broadly understanding the science and patents at play in the arena.

Once we understand the context-specific lifecycle of biofilms in each situation, open innovation principles can apply focus and discipline to define, search for and find relevant solutions. We know that bacterial and ecological factors influence the establishment and virulence of biofilms. Understanding these factors helps us to find novel targets for biofilm interventions, including:

• Preventive strategies: these target adhesion of planktonic bacteria to a substrate and to each other. Extrinsic factors such as surface chemistry, nutrient availability and flow velocity, can modulate adhesion mechanisms. For example, smart surface strategies such as the liquid repellent, low-friction surface technology are essential to keeping medical devices sterile by preventing the attachment and formation of Pseudomonas aeruginosa and Staphylococcus aureus biofilms.

• Disruptive strategies: these typically target the complex three-dimensional structure of the biofilm, which shields the microbes from antibiotics and creates the different microenvironments essential for the growth of multiple species. We can degrade the protective extracellular matrix by using dispersal agents such as dispersin B, nitric oxide and cis-2-decenoic acid, breaking up the biofilm structure and dispersing the biofilm components.

• Treatment strategies: these focus on the interaction and communication between microbial cells making up the biofilm. Often, the goal is not to eradicate the entire biofilm, but to keep the population of beneficial species, while restricting the growth of harmful species, such as in human microbiomes. For example, by modulating the availability of nutrients such as iron or by targeting the cell-to-cell communication process called quorum sensing using compounds such as furanone, the growth of pathogenic species and its attachment to beneficial species can be disrupted in oral mucosal surfaces, thereby decreasing bacterial virulence and preventing the onset of periodontitis.

Innovation opportunities offer a chance to provide value

We can also look for intervention points in the growth and development of biofilms to target potential contamination. A deep understanding of biofilm development will help us to find multiple novel targets to control biofilm infections, contaminations and associated issues. While the relevant bacterial species, biofilm structure, and ecological factors vary from oral care to medical device infection to kitchen surface stains, the basic principles underlying biofilm formation and development are quite similar across domains and can hasten our understanding of intervention targets for new application areas.

Scientific research on biofilms is nascent, but rapidly growing. Companies that are the first to harness this disruption can take the lead in this infection and contamination market.

Innovation opportunities in the development of a successful biofilm prevention and disruption include:

• Developing a deeper understanding of the specific commensal and pathogenic species involved
• Identifying extrinsic factors affecting differential colonisation and growth of relevant microbial species
• Examining the influence of host factors on the ecology of biofilm growth
• Investigating the multiple potential intervention points that exist in the many biological processes underlying the establishment, growth and homeostasis of the biofilms
• Deterring the anaerobes by changing environmental or surface factors to those unfavourable for their growth
• Prevention of adhesion of the colonising organisms
• Identifying and targeting the intermediary strains that aid the colonisation and growth of pathogenic organisms
• Interfering with microbial communication – especially quorum sensing – which is critical to colonisation and growth of pathogenic microbes.

Answers may hide in unexpected places

You may find solutions where you least expect them. For instance, IBM’s nano-medicine programme has invented a hydrogel that could prevent and destroy biofilm infections on catheters. And an enzyme, NucB, isolated from a marine bacterium growing on the surface of seaweeds may breakdown extracellular DNA of medical biofilms and disperse them.

Microbial biofilms have significant and costly detrimental effects across a variety of industries. Companies can realise value if they understand that biofilm infections and contaminations are increasingly resistant to currently available antiseptics and antibiotics and require innovative anti-biofilm technologies. By using scientific insights to guide to their own R&D, businesses have the potential to create effective anti-biofilm solutions.