Inhaled predatory bacteria-loaded large porous microspheres to eradicate drug-resistant Pseudomonas aeruginosa from the lung

The pneumonia caused by antimicrobial-resistant Gram-negative bacteria is an intractable clinical problem due to the lack of effective treatments. Inspired by the unique predatory bacterial ability of <i>Bdellovibrio bacteriovorus</i>, we here developed an inhalable live bacterial formulations, i.e., <i>B. bacteriovorus</i>-loaded poly(lactic-co-glycolic acid) (PLGA) large porous microspheres (BPMs), to eradicate antimicrobial-resistant <i>Pseudomonas aeruginosa</i> from the lung. BPMs serve as a "safe house" of <i>B. bacteriovorus</i> to avoid being phagocytized by macrophages due to their large size; while the continual release of <i>B. bacteriovorus</i> at the infection site is achieved. We proved BPMs had good biosafety, pulmonary inhalation properties, and antimicrobial effects. The infected mice showed reduced inflammation and lung injury and their respiratory function was well recovered. BPMs have great potential as dry powder inhalers for the treatment of bacterial pneumonia. Inhaled BPMs are an effective treatment against drug-resistant bacterial pneumonia and this live medication is expected to be an alternative therapy to antibiotics.