Diversification of Orientia tsutsugamushi genotypes by intragenic recombination and their potential expansion in endemic areas

Abstract

BackgroundScrub typhus is a mite-borne febrile disease caused by O. tsutsugamushi infection. Recently, emergence of scrub typhus has attracted considerable attention in several endemic countries in Asia and the western Pacific. In addition, the antigenic diversity of the intracellular pathogen has been a serious obstacle for developing effective diagnostics and vaccine.Methodology/Principal findingsTo understand the evolutionary pathway of genotypic diversification of O. tsutsugamushi and the environmental factors associated with the epidemiological features of scrub typhus, we analyzed sequence data, including spatiotemporal information, of the tsa56 gene encoding a major outer membrane protein responsible for antigenic variation. A total of 324 tsa56 sequences covering more than 85% of its open reading frame were analyzed and classified into 17 genotypes based on phylogenetic relationship. Extensive sequence analysis of tsa56 genes using diverse informatics tools revealed multiple intragenic recombination events, as well as a substantially higher mutation rate than other house-keeping genes. This suggests that genetic diversification occurred via frequent point mutations and subsequent genetic recombination. Interestingly, more diverse bacterial genotypes and dominant vector species prevail in Taiwan compared to other endemic regions. Furthermore, the co-presence of identical and sub-identical clones of tsa56 gene in geographically distant areas implies potential spread of O. tsutsugamushi genotypes.Conclusions/SignificanceFluctuation and diversification of vector species harboring O. tsutsugamushi in local endemic areas may facilitate genetic recombination among diverse genotypes. Therefore, careful monitoring of dominant vector species, as well as the prevalence of O. tsutsugamushi genotypes may be advisable to enable proper anticipation of epidemiological changes of scrub typhus.

Ecological and microbiological diversity of chigger mites, including vectors of scrub typhus, on small mammals across stratified habitats in Thailand

“…The diverse microbiomes of chiggers add a further layer to the network of potential interactions that Orientia is exposed to, and future studies should determine whether some of these commensal bacteria affect chigger vector competence. Moreover, the positive correlation we identified here between chigger species richness and scrub typhus incidence deserves further investigation in other endemic countries, especially in relation to the epidemiology of Orientia strain diversity [48].…”

“…Moreover, more than 20 species of Leptotrombidium have been reported from Thailand, many only from the northern provinces where scrub typhus incidence is highest [13]. Although the majority of these species are not known to be scrub typhus vectors, recent data on vector competence are lacking, and it is plausible that transmission of O. tsutsugamushi by two or more vectors in the same region may contribute to diversification of the pathogen and an increase in human cases, as has been recently hypothesised for Taiwan [45, 48]. We also observed that human scrub typhus incidence was negatively associated with host-parasite network connectance, suggesting that increasing complexity of chigger-host interactions might reduce human exposure by zooprophylaxis, or lead to a greater likelihood that non-vector species dominate networks.…”

Targeting metabolic pathways proteins of Orientia tsutsugamushi using combined hierarchical approach to combat scrub typhus

“…Orientia is an important bacterial pathogen with higher risk of infection for human population. Around one third of the population in the world is at risk of attaining the infection of Ott , emphasizing the importance of pathogen in global health . It was previously documented that metabolic pathway proteins are best suitable drug or vaccine targets .…”

“…Around one third of the population in the world is at risk of attaining the infection of Ott, emphasizing the importance of pathogen in global health. 52 It was previously documented that metabolic pathway proteins are best suitable drug or vaccine targets. 53 Few studies were performed in order to search protein targets in Ott 54 ; however, unique pathway proteins of Ott have not been analyzed till date for therapeutic targets.…”

Evaluation of Enzyme-Linked Immunosorbent Assay Using Recombinant 56-kDa Type-Specific Antigens Derived from Multiple Orientia tsutsugamushi Strains for Detection of Scrub Typhus Infection

“…15 Recent studies also indicated that more divergent genotypes of O. tsutsugamushi prevail in Taiwan compared with other endemic countries in the Asian-Pacific region. 16,17 Therefore, it is necessary to consider the impact of broad genetic diversity of TSA gene of O. tsutsugamushi strains on diagnosis of scrub typhus in Taiwan.…”