Editors' ChoiceInfectious Disease

Therapy going viral

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Science Translational Medicine  08 Aug 2018:
Vol. 10, Issue 453, eaau7384
DOI: 10.1126/scitranslmed.aau7384


Virus-loaded microparticles can successfully treat lung infections in mice.

Community-acquired lung infections, such as pneumonia, represent the most common cause of death from infectious disease in the United States. Lung infection also affects approximately 29,000 cystic fibrosis patients annually in the United States. Yet eradication of these infections is limited by antibiotic dosing and antibiotic-resistant bacteria. Recently it has been shown that bacteriophages (viruses that specifically target and lyse bacteria) can be used to treat acute lung infections; however, delivery and fabrication methods hinder phage stability and function. Agarwal and colleagues designed phage-loaded microparticles to overcome these issues.

By delivering a mixture of phages that target Pseudomonas aeruginosa (bacterium recognized as the primary cause of morbidity and mortality in lung infections), they showed phages could be effective in treating infected wild-type and cystic fibrosis mouse models. The phage-loaded microparticles, inhaled in dry powder form, were deposited throughout the lung, and the phages were delivered in an active state. P. aeruginosa-infected wild-type mice treated with phage-loaded microparticles showed 100% survival over six days compared with only 13% survival for untreated mice. Phage-loaded microparticles reduced bacterial counts by an order of magnitude compared with controls in lung assays conducted 24 hours after microparticle delivery. In a similar experiment using a mouse model of cystic fibrosis, phage-loaded microparticles reduced bacterial counts by three orders of magnitude compared with controls.

This study also showed that phage-loaded microparticles were effective in targeting clinical strains of bacteria that caused acute lung infections in wild-type mice. Though further research is warranted in larger animals and to examine the performance of phage-loaded microparticles in chronic infections, the work of Agarwal and colleagues could signify a major advance in the treatment of acute lung infections. The dry formulation of phage-loaded microparticles could promise easy clinical administration using inhalers that would have a long shelf life. The effective delivery of active phage-loaded microparticles that kill host bacteria in the lungs represents great translational potential.

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