Invasion and Persistent Intracellular Colonization of Erythrocytes

Abstract

The expanding genus Bartonella includes zoonotic and human-specific pathogens that can cause a wide range of clinical manifestations. A productive infection allowing bacterial transmission by blood-sucking arthropods is marked by an intraerythrocytic bacteremia that occurs exclusively in specific human 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 may permit the design of strategies to control the reservoir and transmittable stages of these emerging pathogens. We have dissected the process of Bartonella erythrocyte parasitism in experimentally infected animals using a novel approach for tracking blood infections based on flow cytometric quantification of green fluorescent protein–expressing bacteria during their interaction with in vivo–biotinylated erythrocytes. Bacteremia onset occurs several days after inoculation by a synchronous wave of bacterial invasion into mature erythrocytes. Intracellular bacteria replicate until reaching a stagnant number, which is sustained for the remaining life span of the infected erythrocyte. The initial wave of erythrocyte infection is followed by reinfection waves occurring at intervals of several days. Our findings unravel a unique bacterial persistence strategy adapted to a nonhemolytic intracellular colonization of erythrocytes that preserves the pathogen for efficient transmission by blood-sucking arthropods.

Strategies of exploitation of mammalian reservoirs by Bartonella species

“…However, although the endothelial vasculature undeniably plays a role in the early stages of infection, there is some experimental evidence that other putative cell types, such as erythrocytic precursors, may also serve as a niche for infecting bartonellae [29]. This hypothesis, however, conflicts with data obtained using the GFP- B. tribocorum- rat model that clearly indicated that encounter with, and invasion of, erythrocytes occurs in the bloodstream [3]. Furthermore, we have been unable to find any evidence for the presence of bartonellae in erythrocyte precursors isolated from the bone marrow of B. birtlesii -infected mice, despite rigorous efforts to do so (unpublished observations).…”

The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae

“…Likewise, genes involved in hemin biosynthesis are present in Rickettsia but absent from Bartonella. Also, these differences correlate with lifestyle characteristics; Bartonella parasitizes erythrocytes (10)(11)(12) and is suggested to acquire essential iron molecules from the heme moiety of hemoglobin. Consistently, B. quintana and B. henselae have the highest reported hemin requirement for bacterial growth in vitro (39), and no genes for hemin biosynthesis were identified in either genome.…”

“…In contrast, B. quintana contains only 18 repeat families, 12 of which are two-member families. The largest family in B. quintana contains seven tandemly repeated copies of the trwL gene located in one of the two operons coding for putative type IV secretion systems (12), and the second largest is a family of hemin-binding proteins (31).…”

“…Experimental animal infection models suggest that the initial infection in the host is in a yet unknown niche, from which erythrocytes are periodically seeded (10)(11)(12). The VirB͞VirD type IV secretion system is required at an early stage of the infection, possibly for colonization of the primary niche (11).…”

A family of variably expressed outer-membrane proteins (Vomp) mediates adhesion and autoaggregation in Bartonella quintana

“…Another Bartonella persistence strategy is invasion of and residence in the intracellular compartment of nonphagocytic host cells (9,10). Binding of Bartonella to different host-cell types likely involves adhesins that are variably expressed, but the Bartonella adhesins that are involved have not been identified definitively.…”