Researchers have found Small Colony Variants (SCVs) of Pseudomonas aeruginosa to be a hallmark of chronic infection in cystic fibrosis (CF) patients. The findings published in the journal PLoS Pathogens suggest that SCV-mediated persistence might be a good target for antimicrobial chemotherapy.
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 antibiotic resistance, they have long been suspected of mediating the P. aeruginosa persistence phenotype in CF infections.
In the study, researchers characterized a signaling system in P. aeruginosa called YfiBNR, mutations 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 casual link between SCV and persistence in chronic P. aeruginosa infections.
The study’s authors concluded that ‘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.”