Invasion and persistent intracellular colonization of erythrocytes: A unique parasitic strategy of the emerging pathogen Bartonella

The expanding genus Bartonella includes zoonotic and human-specific pathoge ns that can cause a wide range of clinical manifestations. A productive inf ection allowing bacterial transmission by blood-sucking arthropods is marke d by an intraerythrocytic bacteremia that occurs exclusively in specific hu man or animal reservoir hosts. Incidental human infection by animal-adapted bartonellae can cause disease without evidence for erythrocyte parasitism. A better understanding of the intraerythrocytic lifestyle of bartonellae m ay permit the design of strategies to control the reservoir and transmittab le stages of these emerging pathogens. We have dissected the process of Bar tonella erythrocyte parasitism in experimentally infected animals using a n ovel approach for tracking blood infections based on flow cytometric quanti fication of green fluorescent protein-expressing bacteria during their inte raction with in vivo-biotinylated erythrocytes. Bacteremia onset occurs sev eral days after inoculation by a synchronous wave of bacterial invasion int o mature erythrocytes. Intracellular bacteria replicate until reaching a st agnant number, which is sustained for the remaining life span of the infect ed erythrocyte. The initial wave of erythrocyte infection is followed by re infection waves occurring at intervals of several days. Our findings unrave l a unique bacterial persistance strategy adapted to non-hemolytic intracel lular colonization of erythrocytes that preserves the pathogen for efficien t transmission by blood-sucking arthropods.