The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo
Mice, Inbred BALB C
Neutropenia
Neutrophils
Mice
Phagocytosis
Pseudomonas aeruginosa
Animals
Pseudomonas Infections
Female
Bacteriophages
Phage Therapy
Pseudomonas Phages
Spleen
Research Article
DOI:
10.1172/jci.insight.181309
Publication Date:
2024-10-25T13:49:08Z
AUTHORS (17)
ABSTRACT
AbstractWith the increasing prevalence of antimicrobial-resistant bacterial infections, there is great interest in using lytic bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage pharmacokineticsin vivoremain poorly understood. Here, we have examined the contribution of neutrophils, the most abundant phagocytes in the body, to the pharmacokinetics of intravenously administered bacteriophage in uninfected mice. A single dose of LPS-5, an antipseudomonal bacteriophage recently used in human clinical trials, was administered intravenously to both wild-type BALB/c and neutropenic ICR mice. Phage concentrations were assessed in peripheral blood and spleen at 0.5, 1, 2, 4, 8, 12, and 24 hours after administration by plaque assay and qPCR. We observed that the phage clearance is only minimally affected by neutropenia. Indeed, the half-life of phages in blood in BALB/c and ICR mice is 3.45 and 3.66 hours, respectively. These data suggest that neutrophil-mediated phagocytosis is not a major determinant of phage clearance. Conversely, we observed a substantial discrepancy in circulating phage levels over time when measured by qPCR versus plaque assay, suggesting that substantial functional inactivation of circulating phages occurs over time. These data indicate that circulating factors, but not neutrophils, inactivate intravenously administered phages.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (42)
CITATIONS (4)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....