New Strategies Needed in Infection & Contamination Control: Spotlight on Anti-Biofilm Technologies

Traditional antibiotics are growing impotent against biofilms that cause medical infections and product contamination. What can companies do to improve medicine, agriculture and everyday life and save billions in health care and contamination costs?

Microbial biofilms are ubiquitous and cause expensive health infections & industrial contaminations
Bacteria or fungi tend to grow as dense colonies (biofilms) over time and become strongly attached to contact surfaces. The biofilm structure provides protection, food and nutrients to the organisms. Depending on the microbial species or where they grow (environmental / biomedical / industrial), biofilms can be either beneficial or detrimental. Biofilms including pathogens or harmful microbes pose a significant threat to a variety of fields like healthcare, food processing, household & industrial cleaning, air & water handling systems. For instance, dental plaque, foggy contact lenses, infected medical implants, sticky fruit surfaces are all consequences of biofilms and cost billions of dollars every year globally in product contamination and medical infections.

Agricultural contaminations are a serious problem because biofilms are not easily removed. Plant diseases caused by microbial biofilms contribute to a loss of an estimated 10% of global food supply. Foodborne illnesses associated with fresh fruits and vegetables have increased dramatically over the past 30 years. Biofilms also lead to livestock infections such as bovine mastitis which costs the US dairy industry about 2 billion dollars annually or 11% of total US milk production.

Biofilms have significant implications on human health ranging from dental caries, infected implants, endocarditis to cystic fibrosis and account for over 80% of microbial infections in the body (ref: US NIH). Dental caries, a consequence of plaque biofilm, is highly prevalent globally and has severe consequences in terms of cost and health. Tooth decay due to caries affects 25% of all toddlers and 50% of all teenagers in the US. In 2010, an estimated $105B was spent on dental care and services in the US (Center for Medicare and Medicaid, 2011), Potentially deadly biofilms are responsible for an estimated 1.7 million hospital acquired infections (HAIs) every year in the US costing hospitals about 11.5 billion dollars in treatment (US CDC, 2007). HAIs such as surgical site infections, nosocomial diarrhea, catheter associated urinary tract infections and central line associated bloodstream infections are a significant cause of patient morbidity and mortality.

iconsIndustries Affected by Infection or Contamination Due to Biofilms

Antiseptics & antibiotics are becoming increasingly ineffective against biofilms and often contribute to development of antimicrobial resistance
Standard commercial infection control strategies, such as antiseptics (eg: bleach, ethanol), biocides (eg: chlorhexidene, triclosan) and antibiotics (eg: ampicillin, penicillin, gentamicin), used in a variety of industries target free-living, planktonic forms of bacteria. In the late 1970s and 1980s, bacterial researchers in academia began to elucidate the biofilm mode of existence for bacteria. Over the course of three decades, researchers have come to understand that biofilms are difficult to eradicate with conventional antimicrobial agents because the biofilm architecture prevents penetration of these agents and protects the individual organisms within from being attacked. Further, the biofilm colonies develop several antimicrobial resistance mechanisms which make them 20-1000 times less sensitive to biocides and antiseptics than free-living planktonic forms. Hence, there is growing concern in academia and the industry over antibiotics and antiseptics fostering multidrug resistance. For these reasons, new or alternative approaches to microbial contamination that are focused on preventing, disrupting or treating biofilm formation and growth are needed. Such technologies have the potential to be very specific, highly effective and environmentally safe and not promote resistance.

diagramBiofilms are a complex matrix providing a protective environment that allows pathogens to flourish.

Prevention, disruption and treatment of biofilm contaminations present a huge underexploited business opportunity
In general, there are over twelve overarching intervention points (bacterial and ecological factors) in the effort to control biofilms. However, not all are equally relevant to every situation. To control, prevent or modify complex biofilm activity and behavior, a multi-disciplinary understanding of its mechanisms of attachment, growth and development and a broad search strategy to identify novel technological solutions are needed. A deep knowledge of biofilms in the context of the specific environment, relevant organisms, and regulatory constraints needs to be built by broadly understanding the science and patent art in the area. Once the context specific lifecycle of biofilms for the specific situation is understood, Open Innovation principles can be utilized to apply focus and discipline to define, search for, and acquire relevant solution technologies.

We know that bacterial and ecological factors influence the establishment and virulence of biofilms. Understanding these factors helps us identify novel targets for biofilm interventions such as the following:

  • Preventive strategies target adhesion of planktonic bacteria to a substrate and to each other. Adhesion mechanisms can also be modulated via extrinsic factors such as surface chemistry, nutrient availability, flow velocity, etc. For example, smart surface strategies such as the liquid repellant, low-friction surface technology (SLIPS) are essential to keeping medical devices sterile by preventing the attachment and formation of Pseudomonas aeruginosa and Staphylococcus aureus biofilms.
  • Disruptive strategies typically target the complex three dimensional structure of the biofilm which shields the microbes from antibiotics and creates different microenvironments essential for the growth of multiple species. By using dispersal agents such as dispersin B, nitric oxide and cis-2-decenoic acid, the protective extracellular matrix is degraded, thereby breaking up the biofilm structure and dispersing the biofilm components.
  • Treatment strategies 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 maintain 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 like 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.

Intervention points in the growth and development of biofilms can be identified to target biofilm contamination.
A deep understanding of biofilm development can help identify 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 expedite 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 nascent domain have the opportunity to disrupt the infection and contamination market (see figure).

graphHarnessing biofilm science presents an opportunity for significant disruptions in combating infections and contaminations.

When considering development of a successful biofilm prevention/disruption strategy, we want to highlight several innovation opportunities:

  • Understand the specific commensal and pathogenic species involved
  • Identify extrinsic factors impacting differential colonization and growth of relevant microbial species
  • Examine the influence of host factors on the ecology of biofilm growth
  • Investigate the multiple potential intervention points that exist in the many biological processes underlying the establishment, growth and homeostasis of the biofilms
  • Evaluate approaches such as:
  • Deterring the anaerobes by changing environmental or surface factors to those unfavorable for their growth
  • Prevention of adhesion of the colonizing organisms
  • Identifying and targeting the intermediary colonizing strains that facilitate colonization and growth of pathogenic organisms
  • Interfering with microbial communication (especially quorum sensing) critical to colonization and growth of pathogenic microbes.
  • Solutions may come from unexpected places; for instance, IBM’s nano-medicine program has invented a hydrogel that is being explored for application to preventing and destroying biofilm infections on catheters. An enzyme, NucB, isolated from a marine bacterium growing on the surface of seaweeds has been shown to breakdown extracellular DNA of medical biofilms and disperse them.

In summary, microbial biofilms have significant and costly detrimental effects across a variety of industries. Companies can realize 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 these insights as an input to their own R&D and commercialization plans, companies can create effective anti-biofilm solutions.

Mekhala Raghavan, PhD

Senior Associate