El Karkouri K et al. (2017), Multi-omics Analysis Sheds Light on the Evoluti...

XB-ART-53894

Front Microbiol 2017 Jul 20;8:1363. doi: 10.3389/fmicb.2017.01363.

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Multi-omics Analysis Sheds Light on the Evolution and the Intracellular Lifestyle Strategies of Spotted Fever Group Rickettsia spp.

El Karkouri K , Kowalczewska M , Armstrong N , Azza S , Fournier PE , Raoult D .

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Arthropod-borne Rickettsia species are obligate intracellular bacteria which are pathogenic for humans. Within this genus, Rickettsia slovaca and Rickettsia conorii cause frequent and potentially severe infections, whereas Rickettsia raoultii and Rickettsia massiliae cause rare and milder infections. All four species belong to spotted fever group (SFG) rickettsiae. However, R. slovaca and R. raoultii cause scalp eschar and neck lymphadenopathy (SENLAT) and are mainly associated with Dermacentor ticks, whereas the other two species cause Mediterranean spotted fever (MSF) and are mainly transmitted by Rhipicephalus ticks. To identify the potential genes and protein profiles and to understand the evolutionary processes that could, comprehensively, relate to the differences in virulence and pathogenicity observed between these four species, we compared their genomes and proteomes. The virulent and milder agents displayed divergent phylogenomic evolution in two major clades, whereas either SENLAT or MSF disease suggests a discrete convergent evolution of one virulent and one milder agent, despite their distant genetic relatedness. Moreover, the two virulent species underwent strong reductive genomic evolution and protein structural variations, as well as a probable loss of plasmid(s), compared to the two milder species. However, an abundance of mobilome genes was observed only in the less pathogenic species. After infecting Xenopus laevis cells, the virulent agents displayed less up-regulated than down-regulated proteins, as well as less number of identified core proteins. Furthermore, their similar and distinct protein profiles did not contain some genes (e.g., ompA/B and rickA) known to be related to rickettsial adhesion, motility and/or virulence, but may include other putative virulence-, antivirulence-, and/or disease-related proteins. The identified evolutionary forces herein may have a strong impact on intracellular expressions and strategies in these rickettsiae, and that may contribute to the emergence of distinct virulence and diseases in humans. Thus, the current multi-omics data provide new insights into the evolution and fitness of SFG virulence and pathogenicity, and intracellular pathogenic bacteria.

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Species referenced: Xenopus laevis
Genes referenced: prg4 zbtb7b

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	Figure 1. Phylogenomic tree and, biologic, pathogenic, genomic, and proteomic features, of four SFG Rickettsia species. Bootstrap supports higher than 90% are shown at the nodes. *Means that the total of the detected MS/MS proteins corresponded to genes which are either split or fragment.
	Figure 2. Venn diagrams summarizing pan-genome of the virulent R. slovaca Rsl and the milder R. raoultii Rra causing SENLAT, and the virulent R. conorii Rco and the milder R. massiliae Rma causing MSF.
	Figure 3. Comparative genomics of 9 complete genes (≥60 aa in sizes) distinguishing the virulent R. slovaca and R. conorii from the milder R. raoultii and R. massiliae (A) and 28 complete genes (≥60 aa in sizes) distinguishing the milder R. raoultii and R. massiliae from the virulent R. slovaca and R. conorii (B), with 25 Rickettsia species. Red, green, light blue, and dark blue colors mean that genes can be either complete, split, fragment and absent/remnant, respectively.
	Figure 5. Hierarchical clustering of total protein quantities (fmol μg−1) in the two virulent species R. slovaca Rsl and R. conorii Rco, and, the two milder species R. raoultii Rra and R. massiliae Rma, as classified by COG functional categories.
	Figure 6. Protein profiles obtained between the SENLAT agents (the virulent R. slovaca Rsl/the milder R. raoultii Rra), and between the MSF agents (the virulent R. conorii Rco/the milder R. massiliae Rma), as classified by COG functional categories. Up, Down and Specific mean up-regulated down-regulated and specific proteins.
	Figure 7. Similar and distinct protein patterns obtained between the SENLAT agents (the virulent R. slovaca Rsl/the milder R. raoultii Rra) and the MSF agents (the virulent R. conorii Rco/the milder R. massiliae Rma), as classified by COG functional categories. Up, Down, Equally, Specific and Un-classified mean up-regulated, down-regulated, equally regulated, specific and un-classified proteins, respectively.
	Figure 8. Summary of multi-omics results obtained from comparative analyses between four SFG rickettsiae including the virulent R. slovaca Rsl and the milder R. raoultii Rra which cause SENLAT diseases as well as the virulent R. conorii Rco and the milder R. massiliae Rma which cause MSF diseases. Up, Down, Equally, Specific and Un-classified mean up-regulated, down-regulated, equally regulated, specific and un-classified proteins, respectively. As an example, Non up means that the proteins can be either down-regulated, equally regulated, specific or un-classified proteins. Red and blue colors correspond to the most virulent and the milder agents, respectively. Overall, the two most virulent agents compared with the milder agents exhibited several driving forces that may be associated to differences in virulence and/or plasticity including divergent and reductive evolution, no plasmid, high structural variations and/or a lack of genes in the mobilome. The similarities in the disease (i.e., either SENLAT or MSF) between two distantly related species suggest a convergent evolution. Moreover, the virulent agents also displayed similar and distinct protein profiles mainly in six COG categories. These patterns may include putative virulence- and/or disease-associated proteins as well as putative antivirulence-related proteins of the milder agents.
	Figure 4. Venn diagrams summarizing pan-proteome of the virulent R. slovaca Rsl and the milder R. raoultii Rra causing SENLAT, and the virulent R. conorii Rco and the milder R. massiliae Rma causing MSF.

References [+] :

Akama, Whole-genome tiling array analysis of Mycobacterium leprae RNA reveals high expression of pseudogenes and noncoding regions. 2009, Pubmed