**4. Biofilm**

The pathogen colonized as planktonic form, and the cells convert to the sessile state to form biofilms. The hydrated structured matrices made up of exopolysaccharides and proteins, having 'slimy' characteristic can form on many surfaces from catheters to prokaryotic cells and eukaryotic. The main cause of persistent chronic infections is biofilm formation is essentially impenetrable inhabitants are protective for the bacterial strains from biocides [11]. The only one treatment to deal this situation is physical removal of the biofilm through surgery. Biofilms have heterogeneous populations of intra-species (phenotype and genotype, growth) and inter-species diversification. *P. aeruginosa* may be as dominant pathogen or with other pathogens such as Gram-negative *Burkholderia cenocepacia* and Gram-positive *S. aureus* [12]. The heterogeneous bacterial population of *P. aeruginosa* show distinct microenvironments for biofilms [13]. Metabolically active cells are at periphery and consume most of the oxygen, causing oxygen gradients in the biofilm [14]. The deeper layers of the biofilm have less metabolically active bacteria and are hypoxic. The actively growing peripheral bacterial cells of biofilms mostly susceptible to antibiotics or to the provided the drug which can penetrate slimy layer of the biofilm. Presence of a single polar flagellum made *P. aeruginosa* as motile. *P. aeruginosa is* exhibiting three distinctive types of motility and all of these types are required for development of biofilm which are;


[15–20] (**Figure 2**).

**Figure 2.** *Different stages of the biofilm development. Modified from [21].*
