Orientia and Rickettsia: different flowers from the same garden

Gillespie, Joseph J.; Salje, Jeanne

doi:10.1016/j.mib.2023.102318

“…Compared with Rickettsia spp., which synthesize a canonical PGN layer ( 54 , 55 ), the presence of a minimal cell wall in Ot and Anaplasmataceae species is consistent with the absence of rvhB1 from these genomes ( 56 , 57 ). These collective differences in rvh T4SS architecture present clear convergent evolution in Ot and Anaplasmataceae species in the context of shared cell wall morphology and probable responses to host cell immune pressures ( 58 ).…”

Section: Resultsmentioning

confidence: 99%

Orientia tsutsugamushi: comprehensive analysis of the mobilome of a highly fragmented and repetitive genome reveals the capacity for ongoing lateral gene transfer in an obligate intracellular bacterium

Giengkam,

Kullapanich,

Wongsantichon

et al. 2023

mSphere

Self Cite

View full text Add to dashboard Cite

The rickettsial human pathogen Orientia tsutsugamushi (Ot) is an obligate intracellular Gram-negative bacterium with one of the most highly fragmented and repetitive genomes of any organism. Around 50% of its ~2.3-Mb genome is composed of repetitive DNA that is derived from the highly proliferated Rickettsiales amplified genetic element (RAGE). RAGE is an integrative and conjugative element (ICE) that is present in a single Ot genome in up to 93 copies, most of which are partially or heavily degraded. In this report, we analyzed RAGEs in eight fully sequenced Ot genomes and manually curated and re-annotated all RAGE-associated genes, including those encoding DNA mobilization proteins, P-type ( vir ), and F-type ( tra ) type IV secretion system (T4SS) components, ankyrin repeat- and tetratricopeptide repeat-containing effectors, and other piggybacking cargo. Originally, the heavily degraded Ot RAGEs have led to speculation that they are remnants of historical ICEs that are no longer active. Our analysis, however, identified two Ot genomes harboring one or more intact RAGEs with complete F-T4SS genes essential for mediating ICE DNA transfer. As similar ICEs have been identified in unrelated rickettsial species, we assert that RAGEs may play an ongoing role in lateral gene transfer within the Rickettsiales. We also identified a conserved set of gene transfer agent genes in all Ot genomes. Together these findings indicate that, despite their obligate intracellular lifestyle and host range restricted to mites, rodents, and humans, Ot genomes are highly dynamic and shaped through ongoing invasions by mobile genetic elements and virus-like elements. IMPORTANCE Obligate intracellular bacteria, or those only capable of growth inside other living cells, have limited opportunities for horizontal gene transfer with other microbes due to their isolated replicative niche. The human pathogen Ot, an obligate intracellular bacterium causing scrub typhus, encodes an unusually high copy number of a ~40 gene mobile genetic element that typically facilitates genetic transfer across microbes. This proliferated element is heavily degraded in Ot and previously assumed to be inactive. Here, we conducted a detailed analysis of this element in eight Ot strains and discovered two strains with at least one intact copy. This implies that the element is still capable of moving across Ot populations and suggests that the genome of this bacterium may be even more dynamic than previously appreciated. Our work raises questions about intracellular microbial evolution and sounds an alarm for gene-based efforts focused on diagnosing and combatting scrub typhus.

show abstract

“…Understanding cellular immune responses in the major target organs and during acute stages of infection with different Ot strains has been difficult and requires urgent attention. For example, our understanding of the physiologic, antigenic, and virulence differences between Karp and Gilliam strains is very limited, partially due to the complexity and diversity of Ot genome landscapes and the lack of PLOS NEGLECTED TROPICAL DISEASES adequate genetic tools for bacterial manipulation [44,45]. In this study, we conducted a detailed investigation in murine models with these two clinically important Ot strains and revealed pulmonary innate and cellular immune responses in the context of distinct clinical outcomes of disease in B6 mice.…”

Section: Discussionmentioning

confidence: 99%

Differential cellular immune responses against Orientia tsutsugamushi Karp and Gilliam strains following acute infection in mice

Thiriot,

Liang,

Gonzales

et al. 2023

PLoS Negl Trop Dis

3

0

View full text Add to dashboard Cite

Scrub typhus is a leading cause of febrile illness in endemic countries due to infection with Orientia tsutsugamushi (Ot), a seriously understudied intracellular bacterium. Pulmonary involvement associated with vascular parasitism in patients is common and can develop into life threatening interstitial pneumonia. The diverse antigenicity of Ot genotypes and inter-strain differences in genome content are connected to varied virulence and clinical outcomes; however, detailed studies of strain-related pulmonary immune responses in human patients or small animal models of infection are lacking. In this study, we have used two clinically prevalent bacterial strains (Karp and Gilliam) to reveal cellular immune responses in inflamed lungs and potential biomarkers of disease severity. The results demonstrate that outbred CD-1 mice are highly susceptible to both Karp and Gilliam strains; however, C57BL/6 (B6) mice were susceptible to Karp, but resistant to Gilliam (with self-limiting infection), corresponding to their tissue bacterial burdens and lung pathological changes. Multicolor flow cytometric analyses of perfused B6 mouse lungs revealed robust and sustained influx and activation of innate immune cells (macrophages, neutrophils, and NK cells), followed by CD4+ and CD8+ T cells, during Karp infection, but such responses were greatly attenuated during Gilliam infection. The robust cellular responses in Karp-infected B6 mice positively correlated with significantly early and high levels of serum cytokine/chemokine protein levels (CXCL1, CCL2/3/5, and G-CSF), as well as pulmonary gene expression (Cxcl1/2, Ccl2/3/4, and Ifng). In vitro infection of B6 mouse-derived primary macrophages also revealed bacterial strain-dependent immune gene expression profiles. This study provided the lines of evidence that highlighted differential tissue cellular responses against Karp vs. Gilliam infection, offering a framework for future investigation of Ot strain-related mechanisms of disease pathogenesis vs. infection control.

show abstract

“…Compared with Rickettsia spp., which synthesize a canonical PGN layer 56,57 , the presence of a minimal cell wall in Ot and Anaplasmataceae species is consistent with the absence of rvhB1 from these genomes 58,59 . These collective differences in rvh T4SS architecture present clear convergent evolution in Ot and Anaplasmataceae species in the context of shared cell wall morphology and probable responses to host cell immune pressures 60 .…”

Section: The Impact Of Pervasive Mobile Genetic Elements On the Ot Ge...mentioning

confidence: 95%

Orientia tsutsugamushi:analysis of the mobilome of a highly fragmented and repetitive genome reveals ongoing lateral gene transfer in an obligate intracellular bacterium

Giengkam¹,

Kullapanich²,

Wongsantichon³

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

The rickettsial human pathogen Orientia tsutsugamushi (Ot) is an obligate intracellular Gram-negative bacterium with one of the most highly fragmented and repetitive genomes of any organism. Around 50% of its ~2.3 Mb genome is comprised of repetitive DNA that is derived from the highly proliferated Rickettsiales amplified genetic element (RAGE). RAGE is an integrative and conjugative element (ICE) that is present in a single Ot genome in up to 92 copies, most of which are partially or heavily degraded. In this report, we analysed RAGEs in eight fully sequenced Ot genomes and manually curated and reannotated all RAGE-associated genes, including those encoding DNA mobilisation proteins, P-type (vir) and F-type (tra) type IV secretion system (T4SS) components, Ankyrin repeat- and tetratricopeptide repeat-containing effectors, and other piggybacking cargo. Originally, the heavily degraded Ot RAGEs led to speculation that they are remnants of historical ICEs that are no longer active. Our analysis, however, identified two Ot genomes harbouring one or more intact RAGEs with complete F-T4SS genes essential for mediating ICE DNA transfer. As similar ICEs have been identified in unrelated rickettsial species, we assert that RAGEs play an ongoing role in lateral gene transfer within the Rickettsiales. Remarkably, we also identified in several Ot genomes remnants of prophages with no similarity to other rickettsial prophages. Together these findings indicate that, despite their obligate intracellular lifestyle and host range restricted to mites, rodents and humans, Ot genomes are highly dynamic and shaped through ongoing invasions by mobile genetic elements and viruses.

show abstract

Orientia and Rickettsia: different flowers from the same garden

Cited by 10 publications

References 129 publications

Orientia tsutsugamushi: comprehensive analysis of the mobilome of a highly fragmented and repetitive genome reveals the capacity for ongoing lateral gene transfer in an obligate intracellular bacterium

Orientia tsutsugamushi: comprehensive analysis of the mobilome of a highly fragmented and repetitive genome reveals the capacity for ongoing lateral gene transfer in an obligate intracellular bacterium

Differential cellular immune responses against Orientia tsutsugamushi Karp and Gilliam strains following acute infection in mice

Orientia tsutsugamushi:analysis of the mobilome of a highly fragmented and repetitive genome reveals ongoing lateral gene transfer in an obligate intracellular bacterium

Contact Info

Product

Resources

About