Gentamicin Treatment in a Murine Infection Model Suggests Extracellular Orientia tsutsugamushi Contributes to Systemic Dissemination

Abstract

Orientia tsutsugamushi, an obligate intracellular bacterial pathogen, infects multiple cell types and disseminates via the blood and lymphatic system to affect various organs in human and other mammalian hosts. This bacterium replicates exclusively within living cells; however, it also exists transiently in a metabolically inactive extracellular form. While infected leukocytes are known contributors to the systemic spread of the bacterium, the role of the inactive extracellular form in dissemination has been unclear. In this study, we demonstrate that extracellular bacteria are present in the cell-free plasma fraction of infected human and murine blood. Furthermore, treatment with gentamicin, a membrane-impermeable antibiotic, significantly reduces systemic bacterial growth in a murine infection model. These findings suggest a potential role for the extracellular form of the bacterium in the spread of infection and raise the possibility of exploring the use of gentamicin to augment conventional antibiotic therapy during scrub typhus infection.