Microbial biofilms are complex communities of microorganisms that are embedded in a self-produced extracellular polymeric substance matrix. Biofilms can form on a variety of surfaces, including biological tissues, medical devices, and environmental surfaces. Biofilms are associated with a wide range of infections, including chronic wounds, medical device infections, and implant infections. Biofilms are difficult to treat with conventional antibiotics because the EPS matrix protects the bacteria from antibiotics and other antimicrobials. In addition, bacteria in biofilms are often metabolically dormant, which makes them less susceptible to antibiotics. As a result of these challenges, there is a growing need for new therapeutic strategies to target and eradicate biofilms. This chapter will discuss some of the current and emerging strategies for targeting microbial biofilms.
Top1. Introduction
Biofilms have been defined as complex microbial associations anchored to abiotic or biotic surfaces. This structure may be formed by a single or multiple microbial species. The cells are embedded in extracellular matrix produced by the biofilms themselves by which they interact with each other and the environment. However, a new definition of biofilm has been proposed taking other physiological attributes of the micro-organisms forming biofilm into account. Therefore, biofilm is defined as a microbiologically derived sessile community characterized by cells that are irreversibly attached to a substratum or interface or each other, are embedded in a matrix of extra cellular polymeric substances that they have produced and exhibit an altered phenotype with respect to growth rate and gene transcription. Biofilm formation has been observed by most of the bacteria found in natural, clinical and industrial settings. The matrix contains several substances such as polysaccharides, proteins and DNA from the microorganisms and this matrix provides structural stability to the biofilm. The biofilm structure provides protection to the cells against host-defense mechanisms, phagocytosis, biocides, hydrodynamic shear forces an antibiotic treatment. Biofilm is considered to be responsible for 65% of all bacterial infections.
Biofilm formation is developed in three main stages (Figure 1):
- (1)
attachment, the cells arrive to the surface and adhere to this surface;
- (2)
growth and maturation, they begin to produce the exopolysaccharide that constitutes the matrix and mature from microcolonies to multilayered cell clusters;
- (3)
detachment, the cells take on a planktonic state and can thereby form biofilm in other settings.
Figure 1. Biofilm Formation is Developed in Three Main Stages
It has been proposed that detachment mechanisms can be divided into two categories: active and passive. Active detachment refers to mechanisms initiated by the bacteria themselves, such as enzymatic degradation of the biofilm matrix, quorum sensing, etc. On the other hand, passive detachment refers to that mediated by external forces such as fluid shear, abrasion and human intervention. It has also been proposed that the detachment process may be caused by bacteriophage activity within the biofilm.
One of the main properties of bacteria in biofilms is their capacity to be more resistant to antimicrobial agents than planktonic cells. This feature makes it difficult to eradicate infections caused by biofilm forming bacteria, constituting a serious clinical problem.9 Biofilm structures show maximum resistance to antibiotics in the mature stage. (Høiby N, 2010) Several mechanisms are reportedly responsible for the antimicrobial resistance in biofilm structures:
- •
Poor diffusion of antibiotics through the biofilm polysaccharide matrix, although some antibiotics are able to penetrate the matrix;
- •
Physiological changes due to slow growth rate and starvation responses (oxygen, nutrient deprivation or environmental stress);
- •
Phenotypic change of the cells forming the biofilm;
- •
Quorum-sensing, although their exact role is not clear;
- •
The expression of efflux pumps;
- •
Persisted cells: small fractions of persistent bacteria that resist killing when exposed to antimicrobials.