Bacteriophage‐Loaded Poly(lactic‐co‐glycolic acid) Microparticles Mitigate Staphylococcus aureus Infection and Cocultures of Staphylococcus aureus and Pseudomonas aeruginosa

Abstract

Lung infections caused byGram-positive Staphylococcus aureus (S. aureus) and coinfections caused by S. aureus and Gram-negative Pseudomonas aeruginosa (P. aeruginosa) are challenging to treat, especially with the rise in the number of antibiotic-resistant strains of these pathogens. Bacteriophage (phage) are bacteria-specific viruses that can infect and lyse bacteria, providing a potentially effective therapy for bacterial infections. However, the development of bacteriophage therapy is impeded by limited suitable biomaterials that can facilitate effective delivery of phage to the lung. Here, the ability of porous microparticles engineered from poly(lactic-co-glycolic acid) (PLGA), a biodegradable polyester, to effectively deliver phage to the lung, is demonstrated. The phage-loaded microparticles (phage-MPs) display potent antimicrobial efficacy against various strains of S. aureus in vitro and in vivo, and arrest the growth of a clinical isolate of S. aureus in the presence of sputum supernatant obtained from cystic fibrosis patients. Moreover, phage-MPs efficiently mitigate in vitro cocultures of S. aureus and P. aeruginosa and display excellent cytocompatibility with human lung epithelial cells. Therefore, phage-MPs represents a promising therapy to treat bacterial lung infection.

Metapopulation model of phage therapy of an acutePseudomonas aeruginosalung infection

“…Notably, we found that the therapeutic outcome was robust to different distributions of the phage dose across the bronchial network, including heterogeneous and homogeneous dose distributions. This is consistent with outcomes from phage delivery strategies using phage-loaded microparticles to distribute phages throughout the lung, effectively reducing infections caused by P. aeruginosa 39 and S. aureus 40 . Furthermore, Delattre et al developed a computational model that recapitulated phage-bacteria interactions in vivo and found that varying the route of administration of phage dose, i.e., intratracheally or intravenously, did not impact the therapeutic outcome with both courses producing similar effects 36 .…”

Strategies to Promote the Journey of Nanoparticles Against Biofilm‐Associated Infections

“…For the in vivo antibacterial efficacy studies and evaluations of NPs in preclinical, the animal models of the infections remain a gap compared to the actual clinical situation and mainly focus on local infections, such as skin wound, oral, lung and intra-abdominal infections. [249][250][251][252][253][254][255][256][257] New realistic models need to be developed. Additionally, the mechanisms of biofilm recalcitrance and bacteria resistance should be further elucidated in detail.…”

Bacteriophage therapy for drug-resistant Staphylococcus aureus infections

“…Additionally, Kalelkar et al. (2022) developed porous particles from degradable poly(lactic-co-glycolic acid) (PLGA) and successfully delivered a phage cocktail to the lungs of mice, effectively reducing MRSA-induced lung infections.…”