Orientia tsutsugamushi: A life between escapes

Abstract

The life cycle of the mite-borne, obligate intracellular pathogen Orientia tsutsugamushi (Ot), the causative agent of human scrub typhus, differs in many aspects from that of other members of the Rickettsiales order. Particularly, the nonlytic cellular exit of individual Ot bacteria at the plasma membrane closely resembles the budding of enveloped viruses but has only been rudimentarily studied at the molecular level. This brief article is focused on the current state of knowledge of escape events in the life cycle of Ot and highlights differences in strategies of other rickettsiae.

Keywords: Orientia tsutsugamushi; budding; phagosomal escape; scrub typhus.

Figure 1

Intracellular life cycle of Orientia tsutsugamushi (Ot). Schematic overview of the intracellular replication cycle of Ot. Question marks indicate steps with hypothetical interactions and mechanisms.

Figure 2

Endosomal escape and budding‐like cellular exit of Orientia tsutsugamushi (Ot). (a) Ot escapes from late endosomes. T4SS, type IV secretion system. Question marks indicate steps with hypothetical interactions and mechanisms. (b) Cholesterol‐rich lipid rafts (yellow) and the bacterial protein TSA47 (red) are involved in the budding‐like exit of Ot. The lipid and protein composition of the acquired membrane layer are so far unknown. The large inset depicts two hypothetical mechanisms of the budding process, involving the cellular ESCRT machinery (I) or facilitation by bacterial outer membrane proteins (II). EEA1, early endosome antigen 1; ESCRT, endosomal sorting complex required for transport; LAMP2, lysosome‐associated membrane protein 2; TSA47, type‐specific antigen 47.