The intracellular bacterium Rickettsia rickettsii exerts an inhibitory effect on the apoptosis of tick cells

Larissa Almeida Martins, Giuseppe Palmisano, Mauro Cortez, Rebeca Kawahara, José Mario de Freitas Balanco, André Fujita, Beatriz Iglesias Alonso, Darci Moraes Barros-Battesti, Gloria Regina Cardoso Braz, Lucas Tirloni, Eliane Esteves, Sirlei Daffre, Andréa Cristina Fogaça*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
2 Downloads (Pure)


Background: Rickettsia rickettsii is a tick-borne obligate intracellular bacterium that causes Rocky Mountain spotted fever, a life-threatening illness. To obtain an insight into the vector–pathogen interactions, we assessed the effects of infection with R. rickettsii on the proteome cells of the tick embryonic cell line BME26. 

Methods: The proteome of BME26 cells was determined by label-free high-performance liquid chromatography coupled with tandem mass spectrometry analysis. Also evaluated were the effects of infection on the activity of caspase-3, assessed by the hydrolysis of a synthetic fluorogenic substrate in enzymatic assays, and on the exposition of phosphatidyserine, evaluated by live-cell fluorescence microscopy after labeling with annexin-V. Finally, the effects of activation or inhibition of caspase-3 activity on the growth of R. rickettsii in BME26 cells was determined. 

Results: Tick proteins of different functional classes were modulated in a time-dependent manner by R. rickettsii infection. Regarding proteins involved in apoptosis, certain negative regulators were downregulated at the initial phase of the infection (6 h) but upregulated in the middle of the exponential phase of the bacterial growth (48 h). Microorganisms are known to be able to inhibit apoptosis of the host cell to ensure their survival and proliferation. We therefore evaluated the effects of infection on classic features of apoptotic cells and observed DNA fragmentation exclusively in noninfected cells. Moreover, both caspase-3 activity and phosphatidylserine exposition were lower in infected than in noninfected cells. Importantly, while the activation of caspase-3 exerted a detrimental effect on rickettsial proliferation, its inhibition increased bacterial growth. 

Conclusions: Taken together, these results show that R. rickettsii modulates the proteome and exerts an inhibitory effect on apoptosis in tick cells that seems to be important to ensure cell colonization.

Original languageEnglish
Article number603
Pages (from-to)1-14
Number of pages14
JournalParasites and Vectors
Issue number1
Publication statusPublished - 1 Dec 2020
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • Apoptosis
  • Proteome
  • Rickettsiae
  • Tick


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