R Kaur, M Khurana, R K Virk and A Sharma
Biofilm; metals; Nanoparticles; Formulation methods
|PUBLISHED DATE||April 02, 2018|
|PUBLISHER||The Author(s) 2018. This article is published with open access at www.chitkara.edu.in/publications.|
Biofilm refers to a group of microbes colonizing together and often adhered to a surface. The adherence is attributed to secretion of polymeric substances comprising of extracellular DNA, proteins, and polysaccharides thereby limiting the access and inhibitory activity of existing antimicrobial agents. Biofilm are a major cause of acute infections and pose immense clinical threat especially in conditions employing the use of invasive devices thus being a major source of mortality and morbidity. Hence there is a dire need to develop alternative treatment against biofilm related infections. Advances in nanotechnology has opened new horizons. Nanoparticles derived from various metal present promising candidates to ameliorate biofilms owing to their antioxidant potential.
Biofilm is constituted by a colony of microbes that stick together and often attach to a surface. The attachment to biotic or abiotic surface is due to the production of the polymeric substance comprising of extracellular DNA, proteins, and polysaccharides (Donlan, 2002). Biofilm is initiated by adherence of free floating microorganisms to a substratum, if not removed early they anchor permanently by cell adhesion structures such as pili (Fux et. al., 2005). Hydrophobicity contributes immensely in formation of the biofilm by reducing the repulsion between the extracellular surface and microorganism. Cell-cell talk referred to as sensing has been known to be implicated in development of biofilms (Sakuragi and Kolter, 2007). A number of microorganisms like Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, Acinetobacter baumanii etc. produce biofilms. Biofilm formation occurs in stages including intial attachment, irreversible attachment, maturation and dispersal.
Biofilms provide a shield to the parent organisms thus limiting the penetration of antimicrobial compounds and in turn promoting resistance to the same. Biofilms pose a major hazard in clinical conditions involving the use of invasive devices like catheters, prosthetic joints, dental implants etc. that provide an ideal surface for their adherence and growth.
The immune response of the affected person also faces a setback. Antibodies produced as a defence mechanism fail to penetrate owing to matrix binding catalase secreted by biofilm that protect colonized bacteria and inhibit the access to hydrogen peroxide into the film. Other methods of resistance encompass the secretion of enzymes by biofilm that alter or breakdown the antibiotics like lactamases and aminoglycosides, change of cell constituents including cell wall as observed in vancomycin resistance. Impaired antibiotic permeation, nutrient limitation, decreased growth and birth of persister population constitutes the multipronged defense (Stewart, 2002). The presence of efflux pumps impart resistance to several antibiotics classes like tetracycline, betalactams and fluoroquinoles (Sara, 1999).
Various biofilm promoting factors are being researched upon to ameliorate the harmful effect of these clinical biofilms. Biofilm development is controlled by the intracellular adhesion molecule that aids in intercellular adhesion and is a product of icagene (Cramton et. al. 1999). N-acetyl glucosamine-1-phosphate acetyl transferase needed for peptidoglycan, lipopolysaccharide formation. Another target includes Dispersin B, a glycoside hydrolase that cleaves b1®6 N-acetyl glucosamine polymers and is effective against S. aureus, S. epidermalis (Sveltana et. al. 2012). Chelating agents such as sodium citrate, EDTA are useful to ameliorate S. aureus and P. aeruginosa biofilms (Robert and Rodney, 2011). The plant defensins, lytic peptide, anti-adhesion agents such as pillicides are known to play a role in biofilm inhibition.
Another promising strategy against sessile biofilm forming microbes is nanoprticles owing to their their smaller size, high surface area and hence increased penetration potential. Nanoparticles are microscopic particles with at least one dimension less than 100nm. This provides a tremendous driving force for diffusion across the calyx, a property that can be exploited for access through biofilms. The charge of nanoparticles appears to be an essential factor regulating the permeation of nanoparticles (Mahmood et. al., 2013). Among the various types of nanoparticles, metals derivatized into nanoparticulate forms are emerging as potential biofilm scavengers beacuse of high surface area, being stable at increased temperatures and translocation into the cells, etc.
Increased levels of metals ions in a microbial cell leads to oxidative stress and generate hydrogen peroxide, resulting in oxidative damage, decrease in the membrane integrity of microbes, causing leaking out of important cell nutrients, promoting desiccation and subsequent cell death. Metal nanoparticles can bind to protein, in biofilms causing function loss of the bacterial protein, its degradation into non functional moiety. Different metals have been exploited for the formation of nanoparticles, the prominent ones are listed below:
|ISSN||2393-8536, Online : 2393-8544|
In recent past, the occurence of antibiotic resistance has emerged as a serious threat. The situation is significantly serious in treating the biofilm-associated infections, due to the fact that biofilm mode microbes are more resistant to antibiotics as compared to planktonic ones. Hence, its is all the more important to develop novel antimicrobial agents having bactericidal activity.
Presently the use of metal ions and metal nanoparticles has developed as a substitute to the organic compounds as antimicrobial agents. A strong antimicrobial activity is usually associated with nanomaterials, primarily because of the high surface to volume ratio of their constituent particles. This implies a newer application for these nanoparticles as coating agents in medical devices indewelling devices prevent bacterial infections. Moreover, they can find promising applications also in industrial settings as a potential tool to overcome biofouling. Presently the major drawback in the use of metal nanoparticles is the high cost associated with their synthesis. Consequently, a increasing interest has developed in using new eco-friendly processes for the synthesis of metal nanoparticles as biofilm scavangers offers dual benefits of higher penetration and antimicrobial potential.