The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo

• DOI: 10.1172/jci.insight.181309
• Publication Date: 2024-10-25T13:49:08Z
• Authors: Arne Echterhof; Tejas Dharmaraj; Arya Khosravi; Robert McBride; Lynn Miesel; Ju-Hsin Chia; Patrick M. Blanke...; Kun-Yuan Lin; Chien-Chang Shen; Yu-Ling Lee; Yu-Chuan Yeh; Wei Ting Liao; Francis G. Blanke...; Krystyna Dąbrowska; Derek F. Amanatullah; Adam R. Frymoyer; Paul L. Bollyky
• Keywords: Virus quantification; Phage therapy

With the increasing prevalence of antimicrobial-resistant bacterial infections, there is interest in using bacteriophages (phages) to treat such infections. However, factors that govern bacteriophage pharmacokinetics vivo remain poorly understood. Here, we have examined contribution neutrophils, most abundant phagocytes body, i.v. administered uninfected mice. A single dose LPS-5, a recently used human clinical trials drug-resistant Pseudomonas aeruginosa, was both immunocompetent BALB/c and neutropenic CD1 Phage concentrations were assessed peripheral blood spleen at 0.25, 1, 2, 4, 8, 12, 24 hours after administration by plaque assay qPCR. We observed phage clearance only minimally affected neutropenia. Indeed, half-lives phages mice 3.45 3.66 hours, respectively. These data suggest neutrophil-mediated phagocytosis not major determinant clearance. Conversely, substantial discrepancy circulating levels over time when measured qPCR versus assay, suggesting significant inactivation occurs time. indicate alternative factors, but inactivate phages.