Bacterial biofilm and human infectious diseases

Bacterial biofilm and human infectious diseases
 

Department of of Medical Biotechnology and Laboratory Science
Assistant professor Mei-Hui Lin

People may not be familiar with the term "biofilm," but people have certainly encountered biofilm in daily life. If you do not clean the sink or bathtub for a long time, the gunk on surface is biofilm. Previous studies indicated that microorganisms frequently live and proliferate in highly organized, multicellular communities on a solid surface. This microbial lifestyle is referred to as biofilms. The source of extracellular DNA (eDNA) comes from the autolysis of bacteria within the biofilm is important for biofilm formation. Thus, biofilm formation is a process of multicellular behaviors in which bacteria cooperate and communicate each other.
 

In the biofilm, bacteria often cooperate through quorum sensing (QS) to develop unique capabilities to allow themselves survive better in the ecosystem. Quorum sensing is a bacterial cell–cell communication system that allows bacteria to share information and response correlated to population density using chemical signal molecules which are secreted by the bacteria. Biofilm formation occurs through sequential steps in which the initial attachment of planktonic bacteria to a solid surface is followed by their subsequent proliferation, accumulation in multilayer cell clusters. The biofilm cells are held together and protected by a matrix of extracellular polymeric substances (EPS) including polysaccharide, proteins and eDNA. Finally, the mature bacterial community is formed. Once the structure is developed, some bacteria are released into the environment, enabling the biofilm to spread over the surface. In conclusion, the biofilm structure is dynamic.

Fig. 1. Phases of biofilm development in staphylococci. This figure is adapted from
Curr Top Microbiol Immunol. 2008 ; 322: 207–228.)

 

 

S. aureus is an important pathogen and the major causative agent of hospital- and community-acquired infections. This organism is commonly found on the skin, nasopharynx or in the nasal cavities of healthy individuals. The nasal carriage rate is about 25-30% among healthy persons. As a significant part of the normal flora of the human skin and mucous membranes, it is probably easily as a contaminant during the medical procedures and surgical implantation of the polymeric device. In the past two decades, it has been showed that S. aureus is capable of forming biofilm on medical devices including catheters, hip prostheses and artificial heart valves. The bacteria in biofilm may be released into blood and tissue and cause chronic infections and systemic life-threatening diseases. As is generally known, bacteria embedded in the biofilm are extremely resistant to antibiotics and the host immune defense system, which makes medical treatment difficult and impose a high medical financial cost on the economy each year. Once the biofilm formed on a device, the best way to avoid continuing chronic infection is to replace the contaminated devices more frequently that require additional surgery and cause great medical financial losses.
 

 

The device-related infection of S. aureus, which involves biofilm formation, has been considered the most important factor in the pathogenesis of S. aureus infections. Owing to the importance of developing effective strategy in controlling biofilm-associated infection by S. aureus, our research focuses on: 1. The mechanisms of biofilm formation by S. aureus. 2. Selection of natural products which have anti-biofilm activity. 3. Development of anti-biofilm biomaterials. We tested 453 natural compounds on antibiofilm activity against S. aureus and found that a natural product, 1,2,3,4,6-penta-O-galloyl-β-Dglucopyranose (PGG) isolated from the stem of E. oblongifolium, has potent antibiofilm activity. Moreover, coating PGG on polystyrene and silicon rubber surfaces prevents biofilm formation, indicating that PGG is highly promising for clinical use in preventing biofilm formation by S. aureus. The novel characteristics of PGG on antibiofilm activity have been filed for patent application. ROC patent has been granted; US patent, pending. Furthermore, the PGG work also found that iron regulates biofilm formation. To identify more genes that are involved in biofilm formation by S. aureus, we constructed a mutant library, which contains approximately 2000 transposon insertional mutants. From a screening work, many genes which are involved in biofilm formation were identified. The information obtained from this study may reveal the mechanisms that are important to biofilm formation and pathogenesis of S. aureus and be valuable for the development of effective strategies to prevent and control this microorganism in diverse disease settings.