Abstract
Background Rickettsia conorii, the causative agent of the Mediterranean spotted fever, is transmitted to humans by the bite of infected ticks Rhipicephalus sanguineus. The skin thus constitutes an important barrier for the entry and propagation of R. conorii. Given this, analysis of the survival strategies used by the bacterium within infected skin is critical for our understanding of rickettsiosis.Methodology/Principal FindingsHere, we report the first genome-wide analysis of R. conorii gene expression from infected human skin biopsies. Our data showed that R. conorii exhibited a striking transcript signature that is remarkably conserved across patients, regardless of genotype. The expression profiles obtained using custom Agilent microarrays were validated by quantitative RT-PCR. Within eschars, the amount of detected R. conorii transcripts was of 55%, this value being of 74% for bacteria grown in Vero cells. In such infected host tissues, approximately 15% (n = 211) of the total predicted R. conorii ORFs appeared differentially expressed compared to bacteria grown in standard laboratory conditions. These genes are mostly down-regulated and encode proteins essential for bacterial replication. Some of the strategies displayed by rickettsiae to overcome the host defense barriers, thus avoiding killing, were also pointed out. The observed up-regulation of rickettsial genes associated with DNA repair is likely to correspond to a DNA-damaging agent enriched environment generated by the host cells to eradicate the pathogens. Survival of R. conorii within eschars also involves adaptation to osmotic stress, changes in cell surface proteins and up-regulation of some virulence factors. Interestingly, in contrast to down-regulated transcripts, we noticed that up-regulated ones rather exhibit a small nucleotide size, most of them being exclusive for the spotted fever group rickettsiae.Conclusion/SignificanceBecause eschar is a site for rickettsial introduction, the pattern of rickettsial gene expression observed here may define how rickettsiae counteract the host defense.
Highlights
Rickettsia conorii is a Gram-negative bacterium responsible for the Mediterranean spotted fever (MSF), a disease transmitted to humans by the brown dog tick Rhipicephalus sanguineus [1]
While reports of global gene expression profiling in human tissue or noninvasive patient samples suffering from bacterial diseases are limited [8,9], we explored the RNA profiles of R. conorii from eschars collected on MSF patients
The presence of an eschar in rickettsial disease is generally linked with a milder disease as more severe rickettsiosis, namely the Rocky Mountain Spotted Fever (RMSF) and epidemic typhus do not exhibit inoculation eschars [1,2,18]
Summary
Rickettsia conorii is a Gram-negative bacterium responsible for the Mediterranean spotted fever (MSF), a disease transmitted to humans by the brown dog tick Rhipicephalus sanguineus [1]. Within the first 24 hours after the tick attachment, the rickettsiae are already bloodborne and the observed rickettsiae in the tick feeding site and in particular within the eschar are left over rickettsiae undergoing clearance [2] In this respect, the ‘‘tache noire’’ was depicted as being an excellent, accessible model for the study of the humanRickettsia interaction [6]. Rickettsia conorii, the causative agent of the Mediterranean spotted fever, is transmitted to humans by the bite of infected ticks Rhipicephalus sanguineus. Analysis of the survival strategies used by the bacterium within infected skin is critical for our understanding of rickettsiosis
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