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

Abstract

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.

Proteomic analysis of Rickettsia akari proposes a 44 kDa-OMP as a novel biomarker for Rickettsialpox diagnosis

“…These proteomic approaches resulted in the identification of 288 unique proteins that correspond to 28.4% of 1013 protein-coding genes annotated in the R. akari genome. Similar numbers of proteins were identified in previous proteomic studies in which R prowazeki, R. conori, R. raoultii, R. massiliae, R. slovaca and R. parkeri were evaluated [22,[24][25][26]35].…”

Rickettsial genomics and the paradigm of genome reduction associated with increased virulence

“…Twenty-two copies of ankyrin and 11 copies of tetratricopeptide repeats (TPR-repeat), frequently found in endosymbionts [40e43] are found in R. felis [44]. Finally, plasmids are less abundant in virulent than less virulent species [8,24,45]. They were most likely acquired vertically from Orientia/Rickettsia chromosome ancestors [27].…”

“…In addition, recent multi-omics data showed a link between reductive evolution and differential gene expression between two virulent and two less virulent SFG rickettsiae. The two virulent R. conorii (MSF) and Rickettsia slovaca (SENLAT) agents exhibit less up-regulated than down-regulated genes and than the less virulent R. massiliae (MSF) and Rickettsia raoultii (SENLAT) agents [8]. The former two species have more reduced genomes with plasmid loss than the latter two, suggesting that reductive genomic evolution associated with increased virulence may not be only a question of presence or lack of a specific protein but may also result from differential level or degradation of expression of common proteins [8].…”

“…The two virulent R. conorii (MSF) and Rickettsia slovaca (SENLAT) agents exhibit less up-regulated than down-regulated genes and than the less virulent R. massiliae (MSF) and Rickettsia raoultii (SENLAT) agents [8]. The former two species have more reduced genomes with plasmid loss than the latter two, suggesting that reductive genomic evolution associated with increased virulence may not be only a question of presence or lack of a specific protein but may also result from differential level or degradation of expression of common proteins [8]. It was speculated that loss of regulator genes, as observed in several intracellular pathogens, is a critical cause of virulence [45].…”

Proteomic analysis of Rickettsia akari proposes a 44 kDa-OMP as a potential biomarker for Rickettsialpox diagnosis

“…These proteomic approaches resulted in the identi cation of 288 unique proteins that correspond to 28.4% of 1013 proteincoding genes annotated in the R. akari genome. Similar numbers of proteins were identi ed in previous proteomic studies in which R prowazekii, R. conori, R. raoultii, R. massiliae, R. slovaca and R. parkeri were evaluated [22,[24][25][26]35].…”