Pseudomonas aeruginosa is the predominant organism of chronic lung infections in cystic fibrosis (CF) patients. The organism is particularly difficult to treat because of its ability to colonize the lungs of its hosts and form a biofilm. Biofilms are far more resistant to antibiotic therapy than individual bacterial cells. Consequently, patients with CF are especially vulnerable to infection by P. aeruginosa and, despite intensive treatment, the organism is responsible for a high rate of morbidity and mortality.
There are several opportunistic pathogens, such as P. aeruginosa, capable of utilizing their arsenal of virulence factors in an organized fashion. These pathogens have evolved a chemical language referred to as quorum sensing (QS). QS enables bacterial cells to communicate more effectively, to keep track of their numbers and to minimize host responses until sufficient cell numbers have amassed to overwhelm the host immune system. Therefore, despite rigorous antibiotic therapy, CF patients have a life expectancy of about 40 years, with the main cause of death being complications associated with chronic P. aeruginosa infection.
However, there may now be a glimmer of hope in the fight against biofilms that is of particular significance to CF patients. Researchers at the University of Copenhagen and their collaborators have developed a mechanism to identify sources of potential, non-toxic QS-inhibitor compounds in certain foods. The presence of these naturally occurring compounds suggests that diet may offer a more holistic prophylaxis against infection by P. aeruginosa.
Garlic provides benefits to the cardiovascular and immune systems, but it is also an effective anti-fungal, anti-cancer, anti-viral, anti-protozoan and anti-microbial compound. Now, the team of researchers has identified a constituent of garlic that works to block QS-properties required for biofilm formation. The garlic-derived QS-inhibitor, ajoene, is the major constituent of sulfur-containing compounds released when garlic is crushed. During the study, ajoene was found to inhibit the expression of QS-controlled bacterial genes and, furthermore, worked to reduce the production of bacterial rhamnolipid, a key component in shielding biofilms from white blood cells. Moreover, by combining ajoene with tobramycin, the team was able to demonstrate a 90 percent reduction in biofilm forming cells and a rapid clearing of pulmonary P. aeruginosa infection in mice.
With documented success, the team now hopes to find a pharmaceutical partner to develop antimicrobial drugs based on ajoene that will provide a more effective treatment solution for CF patients. The notion of moving beyond the conventional concept of killing bacterial cells to a more dynamic approach of blocking bacterial communication may prove immediately beneficial in the treatment of P. aeruginosa infections, while paving the way for more advanced developments in antibiotic therapy.
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