Author:
Brenner Amanda E.,Muñoz-Leal Sebastián,Sachan Madhur,Labruna Marcelo B.,Raghavan Rahul
Abstract
ABSTRACTBoth symbiotic and pathogenic bacteria in the family Coxiellaceae cause morbidity and mortality in humans and animals. For instance,Coxiella-like endosymbionts (CLEs) improve the reproductive success of ticks — a major disease vector, whileCoxiella burnetiiis the etiological agent of human Q fever and uncharacterized coxiellae cause infections in both animals and humans. To better understand the evolution of pathogenesis and symbiosis in this group of intracellular bacteria, we sequenced the genome of a CLE present in the soft tickOrnithodoros amblus(CLEOA) and compared it to the genomes of other bacteria in the order Legionellales. Our analyses confirmed that CLEOA is more closely related toC. burnetii, the human pathogen, than to CLEs in hard ticks, and showed that most clades of CLEs contain both endosymbionts and pathogens, indicating that several CLE lineages have evolved independently from pathogenicCoxiella. We also determined that the last common ancestor of CLEOA andC. burnetiiwas equipped to infect macrophages, and that even though HGT contributed significantly to the evolution ofC. burnetii, most acquisition events occurred primarily in ancestors predating the CLEOA-C. burnetiidivergence. These discoveries clarify the evolution ofC. burnetii, which previously was assumed to have emerged when an avirulent tick endosymbiont recently gained virulence factors via HGT. Finally, we identified several metabolic pathways, including heme biosynthesis, that are likely critical to the intracellular growth of the human pathogen but not the tick symbiont, and show that the use of heme analogs is a promising approach to controllingC. burnetiiinfections.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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