Treatment of Bacterial Biofilm Infections

Bacterial biofilms now represent the dominant bacterial growth lifestyle in different habitats including natural and clinical environments. Bacterial cells switch between the free-living planktonic mode and the biofilm growth mode, through multiple mechanisms that include adhesion to a substratum, increasing their aggregation into microcolonies and mature biofilms via matrix formation through secretion of extracellular polymeric substances.

Biofilm mode of growth is involved in chronic infections. It is estimated that 65-80% of human infections are due to biofilms, which cause a huge burden on healthcare systems globally.PA is an opportunistic pathogen with the ability to colonize a wide range of hosts and/or substrates and produce biofilms. PA biofilms that are found in cystic fibrosis, chronic obstructive pulmonary disease and chronic infections lead to premature death. Even with biofilms on medically relevant devices such as central venous and urinary catheters, stents, orthopedic prosthesis, mechanical heart valves and contact lenses, such infections remain extremely difficult to treat with a massive impact on healthcare funding.

PA planktonic cells within biofilms demonstrated a slow growth rate that endured many therapeutic doses of antimicrobial agents due to substantially diminished antibiotic diffusions [15-16], and/or cell-mediated host defenses. As a result, the clinical management of those biofilm-ensconced bacteria became intractable. PA played an important role in nosocomial infections, whereas lung cystic fibrosis (CF) is the most common fatal disease. Both the conventional antibiotics and host immune defense often fail to winkle the pathogen out from the lung and increase chronic infections that are punctuated by acute exacerbations of disease and inflammation, usually resulting in lung failure and high morbidity among patients .

However, PA biofilm infections go beyond CF diseases, especially with diabetic patients. As they are vulnerable to chronic wound developments, these wounds lack of healing, and biofilms associated with long-term infection lead to costing tens of thousands of dollars per year for patient. Numerously, PA mucoid phenotype results in lung failure and high morbidity among patients. Beside elastase, extracellular DNA, lipids, extracellular polysaccharide, and rhamnolipids, polysaccharides alginate represents one of the most significant virulence factors for mucoid phenotypes, where culturing CF patients’ sputum showed high amounts of alginate with a reflection of massive production of antibodies against alginates including IgG and IgA classes.

Moreover, antibiotic resistance was attributed to alginate production. These characteristics make biofilms infections extremally difficult to be treated, and this is particularly problematic in hospital accommodation. Establishment of effective antibiofilm strategy represents one of the biggest challenges, because conventional antibiotics are no longer an effective choice for biofilms treatment, but increase the pathogen resistance. Alginate became an executive target to reduce chronic diseases through reducing their viscosity in the clinical cultures by using alginate lyase. It strips biofilms from surfaces, promotes the PA’s killing rate by human immune cells, and improves antipseudomonal antibiotic efficacy. Pseudoalteromonas sp., marine bacteria, that produce exoproducts which exhibit antibiofilm activity against plenty of pathogenic bacteria such as; Salmonella enterica, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis.

The alginate lyase was considered as an approach to improve biofilm treatment. More specifically, alginate forms the main part of biofilm matrix. Hence, we tried during the present study to find an alternative approach to disrupt the biofilm growth mode, and we assumed that alginate lyase may hydrolyze biofilm structure, subsequently making PA14 WT even less resistant to conventional antibiotics and phagocytosis.