Cystic Fibrosis is a chronic, fatal genetic disease that affects the secretory glands that are responsible for the production of fluids like mucus and sweat.The development of CF is the result of a defect in the CF transmembrane conductance regulator (CFTR), a mutationthat runs in families, making the disease an inherited one.
According to the Centers for Disease Control and Prevention there are currently about 30,000 people living with CF in the US and 20,000 in Europe alone. Worldwide, between 70,000 and 100,000 individuals have been diagnosed with CF, though the numbers are likely to be higher.Over 75% of the patients are diagnosed by the age of two. Moreover, statistics reveal that approximately 1,000 new cases of CF are diagnosed each year. CF affects males and females at about the same rate. On the average, individuals with CF have a lifespan of approximately 30 years.
Pseudomonas aeruginosa is recognized as one of the most important pulmonary pathogens and as the predominant cause of morbidity and mortality in CF patients. Indeed, many CF patients eventually become infected with P. aeruginosa. In these cases, their chronic pulmonary infections are characterized by the conversion of the bacteria to a mucoid phenotype, which is characterized by, among other components, a biofilm structure. Once this biofilm develops the infection is almost impossible to clear. This is because surface-anchoring phenotype of the bacteria in the biofilm,engender the establishment of an adaptive microbial habitat that promotes their long-term survival. The body’s struggle to overcome this infection then results in the short lifespan of the CF patients infected with P. aeruginosa. This occurs because biofilm-embedded P. aeruginosa is significantly more tolerant to various antibiotics as well as to the body’s innate and adaptive defense mechanisms. The current therapies are unable to eradicate these P. aeruginosa infections in CF airways is therefore mainly due to antibiotic resistance trait of biofilms. Thus initial colonization of P. aeruginosa in a biofilm should be a key target of novel therapeutic development as early and aggressive therapy can prevent the establishment of these biofilms
Our novel anti-infection compounds were found to be highly active against biofilms of different pathogens including those of P. aeruginosa. Using these compounds has allowed us to develop strategies to prevent the development of or to break up existing biofilm thus making the microbes more susceptible to antimicrobials and to make them easier for clearance by the host immune system, or by therapy directed at preventing a prolonged inflammatory component. Our advanced anti-infection molecules are devoid of bactericidal activity making it an innovative and promising candidate for such a task. This is especially encouraging in light of poor robust evidence regarding the relative effectiveness of any antibiotic preparation evaluated to date for use in CF patients. Our molecules were found to prevent and destroy existing biofilms better than antibiotic treatment by suppressing bacterial virulence behavior and disrupting biofilm formation.