Pathogenic Rickettsia spp. as emerging models for bacterial biology

Abstract

Our understanding of free-living bacterial models like Escherichia coli far outpaces that of obligate intracellular bacteria, which cannot be cultured axenically. All obligate intracellular bacteria are host-associated, and many cause serious human diseases. Their constant exposure to the distinct biochemical niche of the host has driven the evolution of numerous specialized bacteriological and genetic adaptations, as well as innovative molecular mechanisms of infection. Here, we review the history and use of pathogenic Rickettsia species, which cause an array of vector-borne vascular illnesses, as model systems to probe microbial biology. Although many challenges remain in our studies of these organisms, the rich pathogenic and biological diversity of Rickettsia spp. constitutes a unique backdrop to investigate how microbes survive and thrive in host and vector cells. We take a bacterial-focused perspective and highlight emerging insights that relate to new host-pathogen interactions, bacterial physiology, and evolution. The transformation of Rickettsia spp. from pathogens to models demonstrates how recalcitrant microbes may be leveraged in the lab to tap unmined bacterial diversity for new discoveries. Rickettsia spp. hold great promise as model systems not only to understand other obligate intracellular pathogens but also to discover new biology across and beyond bacteria.

Keywords: Rickettsia; bacterial pathogen; model organism; obligate intracellular bacteria.

Fig 1

Clinical and experimental milestones in Rickettsia research. Tn, transposon. ^*Although vaccine candidates have long existed for rickettsioses, there are no approved SFG or TG vaccines in use today.

Fig 2

Phylogenetic position of Rickettsia spp. within bacteria. The tree displays whole genome phylogenies using the indicated species from GTDB (26). The tree was generated with phyloT (https://phylot.biobyte.de/) and plotted with iTOL (https://itol.embl.de/). Note that TRG, AG, and SFG contain additional species than those depicted. ^*R. bellii is considered non-pathogenic in humans.

Fig 3

A roadmap for bacteriological research on Rickettsia spp. Continued technical development and application of new emerging cellular microbiology tools (left) in experiments designed to capture the diversity of Rickettsia spp., their hosts, and their vectors (center) will drastically advance our knowledge of bacterial niche adaptation and fitness mechanisms (right).