Molecular basis for Pseudomonas aeruginosa persistent infections in CF patients

March 12, 2010

New research reveals Small Colony Variants (SCVs) of P. aeruginosa to be a hallmark of chronic infection in cystic fibrosis (CF) patients. Results, published March 12th in the open-access journal PLoS Pathogens, suggest that SCV-mediated persistence might be a good target for antimicrobial chemotherapy.

Cystic fibrosis is a widespread genetic disease that leads to progressive disability and early death. The principal cause of and in CF patients is a progressive deterioration of the respiratory system caused by a chronic infection of the patients' lungs, mainly by the opportunistic bacterial pathogen . CF lung infections can be treated with antibiotics, however full clearance is not possible due to the protective environment of the CF lung and the adaptation of infective species to a persistent lifestyle. This presents serious challenges for the long-term chemotherapy of CF patients.

Adaptive P. aeruginosa morphotypes include SCVs, slow-growing and strongly adherent variants that frequently arise in chronic lung infections. Because the appearance of SCVs correlates with poor lung function and , they have long been suspected of mediating the P. aeruginosa persistence phenotype in CF infections.

In this study, the researchers characterized a signaling system in P. aeruginosa called YfiBNR, mutations in which lead to the generation of SCV variants. Activation of YfiBNR resulted in increased levels of the signaling molecule c-di-GMP, which in turn triggered massive production of exopolysaccharides and drastically reduced growth rates, two hallmarks of SCV behavior. YfiN-mediated SCVs were shown to be highly resistant to macrophage phagocytosis, suggesting a role for the SCV phenotype in immune system evasion. Consistent with this, activation of YfiN significantly increased the persistence of P. aeruginosa in long-term infections in a mouse model, establishing a firm causal link between SCV and persistence in chronic P. aeruginosa infections.

The authors conclude that 'c-di-GMP has long been a key suspect in chronic behavior of bacterial pathogens. The finding that the c-di-GMP-mediated SCV phenotype confers a persistent advantage in mice provides the first direct evidence in favor of such a model. This study thus opens up new avenues to specifically counteract persistent infections.'

Explore further: Garlic hope in infection fight

More information: Malone JG, Jaeger T, Spangler C, Ritz D, Spang A, et al. (2010) YfiBNR Mediates Cyclic di-GMP Dependent Small Colony Variant Formation and Persistence in Pseudomonas aeruginosa. PLoS Pathog 6(3): e1000804. doi:10.1371/journal.ppat.1000804

Related Stories

Garlic hope in infection fight

January 31, 2007

Garlic has been hailed a wonder drug for centuries and has been used to prevent gangrene, treat high blood pressure, ward off common colds and is even believed by some to have cancer-fighting properties.

Research promising for cystic fibrosis

March 18, 2008

New University of Toronto research holds promise for developing innovative therapies against cystic fibrosis and may also serve as a model for future therapies against the HIV virus.

No hiding place for infecting bacteria

March 16, 2009

Scientists in Colorado have discovered a new approach to prevent bacterial infections from taking hold. Writing in the Journal of Medical Microbiology, Dr Quinn Parks and colleagues describe how they used enzymes against ...

Bacteria 'launch a shield' to resist attack

November 2, 2009

Bacteria that cause chronic lung infections can communicate with each other to form a deadly shield against the body's natural defenses. Studying these interactions could lead to new ways of treating bacteria that are resistant ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.