Cystic fibrosis sputum exosomes reduce the ability of neutrophils to kill methicillin-resistant Staphylococcus aureus 9310

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Abstract Description Background Chronic bacterial infections by methicillin-resistant Staphylococcus aureus (MRSA) are a hallmark of cystic fibrosis (CF) lung disease, despite robust neutrophilic inflammation. Also found in high numbers in the CF airway are exosomes. Since exosomes have a wide range of effects in biology, we sought to determine whether exosomes affected the ability of neutrophils to kill MRSA. Methods Exosomes were isolated from the sputum supernatants of two different CF donors (CFBR833 and CFBR 836). Exosomes were then incubated with each of three different CF clinical isolates of MRSA (MRSA25, MRSA24 and MRSA47) for 0.5-1.5 hours. Exosome-treated bacteria were then used to infect healthy or CF human neutrophils. The percent killing of the initial MRSA inoculum was measured after 30 minutes using a microplate-based bacterial growth assay. Results CFBR833 exosomes reduced the killing of MRSA25 by 34% (n = 22), MRSA24 by 30% (n = 7), and MRSA47 by 23% (n = 9). CFBR836 exosomes decreased the killing of MRSA25 by 23% (n = 8), MRSA24 by 30% (n = 7), and MRSA47 by 22% (n = 7). MRSA25 killing by CF neutrophils was 26% (n = 5) less when bacteria were preincubated with CFBR833 exosomes and 30% (n = 3) less when exposed to CFBR836 exosomes. Conclusions Our results indicate that CF sputum-derived exosomes significantly reduce the ability of both healthy and CF neutrophils to kill MRSA. This work gives insight on why MRSA infections are so prevalent in CF and may provide a future therapeutic target Funding Sources Supported by NIH R01 HL136707 (Rada) and NIH R21 5R21A1183057 (Rada) Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

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