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

Richards, Allen L.; Jiang, Ju

doi:10.3390/tropicalmed5020049

Cited by 54 publications

(50 citation statements)

References 84 publications

(131 reference statements)

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Section: Discussionmentioning

confidence: 99%

“…More broadly, investigating the IFN response in the skin may lead us to better understand diseases caused by other arthropod-borne pathogens. One example may be Orientia tsutsugamushi , the causative agent of scrub typhus 41 , a prevalent but poorly understood tropical disease endemic to Southeast Asia 1,42,43 . O. tsutsugamushi also causes eschar formation in humans, but inbred mice do not recapitulate eschar formation during O. tsutsugamushi infection 7 , similar to R. parkeri .…”

Section: Discussionmentioning

confidence: 99%

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Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis

Burke

Engström

Tran

et al. 2020

Preprint

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Arthropod-borne pathogens cause severe human and animal diseases worldwide; however, current animal models are often inadequate in recapitulating key features of infection. Here, we report an intradermal infection model for Rickettsia parkeri, which causes eschar-associated spotted fever rickettsiosis in humans. We show that infection of mice lacking both interferon receptors (Ifnar-/-Ifngr-/-) with R. parkeri causes skin lesion formation similar to human eschars and disseminated disease with as few as 10 bacteria. Using this model, we found that the actin-based motility protein Sca2 is dispensable for R. parkeri survival in organs but is required for R. parkeri dissemination from the skin to peripheral tissues and for causing lethal disease. We also found that immunizing mice with sca2 and ompB mutant R. parkeri protects against subsequent rechallenge with wild-type bacteria. This study characterizes a mouse model that mimics aspects of human rickettsial disease and reveals a pathogenic role for the R. parkeri actin-based motility protein Sca2 in dissemination.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis

Burke

Engström

Tran

et al. 2020

Preprint

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“…Scrub typhus is a re-emerging vector-borne disease prevalent in the Asia-Pacific region ( Kelly et al, 2009 ; Kala et al, 2020 ; Richards and Jiang, 2020 ). It is caused by an obligate intracellular Gram-negative bacterium, namely Orientia tsutsugamushi , which is transmitted to mammalian hosts, including rodents and humans, via Leptotrombidium mites at their larval stage ( Seong et al, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

The Orientia tsutsugamushi ScaB Autotransporter Protein Is Required for Adhesion and Invasion of Mammalian Cells

Nguyen

Kim

et al. 2021

Front. Microbiol.

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Autotransporter proteins are widely present in Gram-negative bacteria. They play a pivotal role in processes related to bacterial pathogenesis, including adhesion, invasion, colonization, biofilm formation, and cellular toxicity. Bioinformatics analysis revealed that Orientia tsutsugamushi, the causative agent of scrub typhus, encodes six different autotransporter genes (scaA–scaF). Although four of these genes (scaA, scaC, scaD, and scaE) are present in diverse strains, scaB and scaF have been detected in only a limited number of strains. Previous studies have demonstrated that ScaA and ScaC are involved in the adherence of host cells. However, the putative function of other O. tsutsugamushi Sca proteins has not been studied yet. In this study, we show that scaB is transcribed and expressed on the surface of O. tsutsugamushi Boryong strain. Using a heterologous Escherichia coli expression system, we demonstrated that ScaB-expressing E. coli can successfully mediate adherence to and invasion into non-phagocytic cells, including epithelial and endothelial cells. In addition, pretreatment with a recombinant ScaB polypeptide inhibits the entry of O. tsutsugamushi into cultured mammalian cells. Finally, we also identified the scaB gene in the Kuroki and TA686 strains and observed high levels of sequence variation in the passenger domains. Here, we propose that the ScaB protein of O. tsutsugamushi can mediate both adhesion to and invasion into host cells in the absence of other O. tsutsugamushi genes and may play important roles in bacterial pathogenesis.

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“…Improved recognition of the disease syndromes by clinicians within the endemic regions and improved more accurate, easy-to-use diagnostics have led in recent years to enhanced recognition. Thus, rickettsioses such as scrub typhus are now being reported within an ever-growing, geographically disparate region [ 6 , 7 ]. In contrast, epidemic typhus caused primarily by Rickettsia prowazekii -infected lice ( Pediculus humanus corporis ) has played a relatively minor role in modern times as a cause of fevers in the AAP.…”

Section: Introductionmentioning

confidence: 99%

A Brief History of the Major Rickettsioses in the Asia–Australia–Pacific Region: A Capstone Review for the Special Issue of TMID

et al. 2020

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The rickettsioses of the “Far East” or Asia–Australia–Pacific region include but are not limited to endemic typhus, scrub typhus, and more recently, tick typhus or spotted fever. These diseases embody the diversity of rickettsial disease worldwide and allow us to interconnect the various contributions to this special issue of Tropical Medicine and Infectious Disease. The impact of rickettsial diseases—particularly of scrub typhus—was substantial during the wars and “police actions” of the last 80 years. However, the post-World War II arrival of effective antibiotics reduced their impact, when recognized and adequately treated (chloramphenicol and tetracyclines). Presently, however, scrub typhus appears to be emerging and spreading into regions not previously reported. Better diagnostics, or higher population mobility, change in antimicrobial policies, even global warming, have been proposed as possible culprits of this phenomenon. Further, sporadic reports of possible antibiotic resistance have received the attention of clinicians and epidemiologists, raising interest in developing and testing novel diagnostics to facilitate medical diagnosis. We present a brief history of rickettsial diseases, their relative importance within the region, focusing on the so-called “tsutsugamushi triangle”, the past and present impact of these diseases within the region, and indicate how historically, these often-confused diseases were ingeniously distinguished from each another. Moreover, we will discuss the importance of DNA-sequencing efforts for Orientia tsutsugamushi, obtained from patient blood, vector chiggers, and rodent reservoirs, particularly for the dominant 56-kD type-specific antigen gene (tsa56), and whole-genome sequences, which are increasing our knowledge of the diversity of this unique agent. We explore and discuss the potential of sequencing and other effective tools to geographically trace rickettsial disease agents, and develop control strategies to better mitigate the rickettsioses.

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

Cited by 54 publications

References 84 publications

Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis

Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis

The Orientia tsutsugamushi ScaB Autotransporter Protein Is Required for Adhesion and Invasion of Mammalian Cells

A Brief History of the Major Rickettsioses in the Asia–Australia–Pacific Region: A Capstone Review for the Special Issue of TMID

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