ROLE OF BACTERIAL BIOFILM IN PERSISTENT INFECTIONS AND CONTROL STRATEGIES

INTRODUCTION Bacterial biofilms can be viewed as a specific type of persistent bacterial infection. After initial invasion, microbes can attach to living and non-living surfaces, such as prosthetics and indwelling medical devices, and form a biofilm composed of extracellular polysaccharides, proteins, and other components. In hosts, biofilm formation may trigger drug resistance and inflammation, resulting in persistent infections. Many bacterial genera like Pseudomonas, Legionella, Streptococcus, Neisseria etc., are found to be involved in formation of biofilms. The objective of this write up is to view clinical aspects of biofilm formation and to suggest strategies to inhibit it. BIOFILM AND INFECTIOUS DISEASES Biofilms are surface bacterial aggregates encased in a synthesized hydrated matrix. These biofilms form a protective covering around the bacteria. This makes the bacteria resistant to host immune system attack. Thus it helps the bacteria to form persistent infection in the host. In general, biofilm formation is a two-stage process that begins with the adherence of bacteria to a substrate surface (Adhesion Stage), and continues by proliferation and differentiation of the attached cells (Maturation Stage). From a molecular biology point of view, these two stages are mainly controlled by surface adhesins and cell-to-cell communication signaling pathways respectively. Adhesins are key regulators of the adhesion stage. Biofilm maturation stage is controlled by quorum sensing systems. Quorum Sensing (QS) is a microbial cell-to-cell communication system designated for cell-density and/or population based gene regulation. Biofilms have been found to be involved in a wide variety of microbial infections in the body. Infectious processes in which biofilms have been implicated include common problems of urinary tract infections, catheter infections, middle-ear infections, formation of dental plaque, gingivitis, coating contact lenses, and less common but more lethal processes such as endocarditis, infections in cystic fibrosis, and infections of permanent indwelling devices such as joint prostheses and heart valves. More recently it has been noted that bacterial biofilms may impair cutaneous wound healing and reduce topical antibacterial efficiency in healing or treating infected skin wounds.

CONTROL STRATEGIES Detection of biofilms is a practical concern. From a clinical point of view, the first step towards a solution for biofilm-related infection is an early positive detection. Biofilm specific antigens and antibodies can be used for the purpose of detection.

After detection of biofilm the next important step is to remove the biofilm formed and to prevent further formation of it. In my view Lectin Pathway of Complement System can be used for clearance of biofilm formed. As we know lectins are proteins that recognize and bind to carbohydrates. Once it binds to carbohydrates or glycoproteins on surface of bacteria, it activates Lectin pathway that finally gives rise to Membrane Attack Complex (MAC) that forms large channel through the membrane of target cell, enabling ions and small molecules to diffuse freely across membrane. This finally leads to lysis of cells. Since the biofilm is also mainly made up of polysaccharides (carbohydrates), Lectin pathway can be used for its disruption. Thus this will lead to clearance of biofilm giving host immune system access to bacteria enclosed within it. The next important stage is to prevent formation of biofilm which can be done by using various strategies. One of the possible strategy can be use of anti-adhesion molecules which will inhibit adhesion stage of biofilm formation. Adhesin analogs can be used as anti adhesin molecules. Dietary inhibitors of adhesion can also be used. Human milk and plant derived products (e.g.lectins) are good example of dietary inhibitors. Quorum Sensing Inhibitors (QSI) can be used as second strategy to inhibit biofilm formation. This will result in breakdown of cell-to-cell communication and the cells will remain in planktonic stage. Furanones and RNA III inhibiting peptides are two main classes of QSI. Another strategy can be to use small peptides which will show antibacterial property towards the biofilm forming bacteria. Certain peptides play an important role in innate immunity of humans. Such peptides can be used to prevent biofilm formation. Neutralizing antibodies raised against the biofilm can also be used as strategy to inhibit biofilm formation.

CONCLUSION Biofilm formation is controlled by surface adhesins and Quorum Sensing mechanism. Biofilm protects the bacteria from attack of host immune system components thereby helping it to establish a persistent infection. Thus biofilm detection and its inhibition are two important clinical aspects. Lectin Pathway can be used for removal of biofilm that has already formed. Different strategies like use of anti-adhesion molecules, QSI, Anti-bacterial peptides and neutralizing antibodies can be used to inhibit formation of biofilms and thus ultimately prevent the infections.

ROLE OF BACTERIAL BIOFILM IN PERSISTENT INFECTIONS AND CONTROL STRATEGIES

MADHAVI SHINDE
M.Sc.BIOTECHNOLOGY PAD, DR.D.Y.PATIL UNIVERSITY NAVI MUMUBAI