Comparative pan-genomic analyses of Orientia tsutsugamushi reveal an exceptional model of bacterial evolution driving genomic diversity

Abstract

Orientia tsutsugamushi, formerly Rickettsia tsutsugamushi, is an obligate intracellular pathogen that causes scrub typhus, an underdiagnosed acute febrile disease with high morbidity. Scrub typhus is transmitted by the larval stage (chigger) of Leptotrombidium mites and is irregularly distributed across endemic regions of Asia, Australia and islands of the western Pacific Ocean. Previous work to understand population genetics in O. tsutsugamushi has been based on sub-genomic sampling methods and whole-genome characterization of two genomes. In this study, we compared 40 genomes from geographically dispersed areas and confirmed patterns of extensive homologous recombination likely driven by transposons, conjugative elements and repetitive sequences. High rates of lateral gene transfer (LGT) among O. tsutsugamushi genomes appear to have effectively eliminated a detectable clonal frame, but not our ability to infer evolutionary relationships and phylogeographical clustering. Pan-genomic comparisons using 31 082 high-quality bacterial genomes from 253 species suggests that genomic duplication in O. tsutsugamushi is almost unparalleled. Unlike other highly recombinant species where the uptake of exogenous DNA largely drives genomic diversity, the pan-genome of O. tsutsugamushi is driven by duplication and divergence. Extensive gene innovation by duplication is most commonly attributed to plants and animals and, in contrast with LGT, is thought to be only a minor evolutionary mechanism for bacteria. The near unprecedented evolutionary characteristics of O. tsutsugamushi, coupled with extensive intra-specific LGT, expand our present understanding of rapid bacterial evolutionary adaptive mechanisms.

Pathogen to commensal? Longitudinal within-host population dynamics, evolution, and adaptation during a chronic >16-year Burkholderia pseudomallei infection

“…Pathogen to commensal evolution during chronic melioidosis exception of two homoplastic SNPs (Fig 3). Consideration of homoplasies and their location in the phylogeny is important for evaluating the degree to which genetic inheritance is clonal or involves lateral gene transfer (LGT) [67][68][69][70]. SNP phylogenies of clonal populations typically have little or no homoplasy, with any character state conflict caused by convergent, Fig 4.…”

Epidemiology and Diversity of Rickettsiales Bacteria in Humans and Animals in Jiangsu and Jiangxi provinces, China

“…Even though it is the only recognized species within the genus Orientia , O . tsutsugamushi exhibits high genetic diversity 45–47 . We identified O .…”

Scrub Typhus: Historic Perspective and Current Status of the Worldwide Presence of Orientia Species

“…Consistent within the Tsutsugamushi Triangle has been the presence of a single species of Orientia which was identified within human cases, vector mites and mammalian hosts [ 8 , 83 , 94 , 98 ]. This species, O. tsutsugamushi, has a diversity of antigenic phenotypes and genetic genotypes found not only between countries but within countries [ 94 , 99 , 100 ]. However, as early as 1951, reports suggesting that scrub typhus occurred outside of the Tsutsugamushi Triangle began to emerge ( Figure 2 ).…”

“…The agents have been molecularly very much the same ( Figure 3 ) from all cases from Chile [ 119 ], except for an imported case from the Republic of Korea, which was determined to be O. tsutsugamushi [ 120 ]. This is quite surprising when considering the extreme variation seen among the O. tsutsugamushi found throughout the Tsutsugamushi Triangle [ 94 , 99 , 100 ]. Similarly, characterization of orientiae from trombiculid mites of the genus Herpetacarus from Chiloé Island found the same orientiae as that associated with scrub typhus cases [ 121 ].…”