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

Author(s):Show less -

Martins, Larissa Almeida ^{[1, 2]} ; Palmisano, Giuseppe ^[1] ; Cortez, Mauro ^[1] ; Kawahara, Rebeca ^{[1, 3]} ; de Freitas Balanco, Jose Mario ^[1] ; Fujita, Andre ^[4] ; Alonso, Beatriz Iglesias ^[1] ; Barros-Battesti, Darci Moraes ^[5] ; Braz, Gloria Regina Cardoso ^[6] ; Tirloni, Lucas ^[2] ; Esteves, Eliane ^[1] ; Daffre, Sirlei ^[1] ; Fogaca, Andrea Cristina ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo, SP - Brazil

^[2] NIAID, Rocky Mt Lab, NIH, Hamilton, MT 59840 - USA

^[3] Macquarie Univ, Dept Mol Sci, Sydney, NSW - Australia

^[4] Univ Sao Paulo, Inst Math & Stat, Dept Computat Sci, Sao Paulo, SP - Brazil

^[5] Sao Paulo State Univ, Dept Vet Pathol, Jaboticabal, SP - Brazil

^[6] Univ Fed Rio de Janeiro, Inst Chem, Dept Biochem, Rio De Janeiro, RJ - Brazil

• Document type: Journal article
• Source: PARASITES & VECTORS; v. 13, n. 1 DEC 1 2020.
• Web of Science Citations: 0

Abstract

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 cellsthat seems to be important to ensure cell colonization. (AU)

• FAPESP's process: 12/24105-3 - Immunobiology of Leishmania spp.: study of the role of CD200 and biogenesis of parasitophorous vacuole in fagocitic cells infected by Leishmania
• Grantee: Mauro Javier Cortez Véliz
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
• Grantee: Giuseppe Palmisano
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 18/18257-1 - Multi-user equipment approved in grant 14/06863-3: HPLC system configured for analysis of carbohydrates, amino acidis, peptides and glycoproteins
• Grantee: Giuseppe Palmisano
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 14/11513-1 - Determination of the differential proteome and lipidome of Amblyomma aureolatum ticks in response to Rickettsia rickettsii infection
• Grantee: Andréa Cristina Fogaça
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/06863-3 - Post-translational modifications in cancer and parasite infection diagnosis: methodological approaches and biological implications
• Grantee: Giuseppe Palmisano
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 14/05855-7 - Determination of the proteome of Rickettsia rickettsii, the etiological agent of Brazilian Spotted Fever
• Grantee: Larissa Almeida Martins
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/26450-2 - Molecular characterization of the interactions among ticks, rickettsiae and vertebrate hosts
• Grantee: Sirlei Daffre
• Support Opportunities: Research Projects - Thematic Grants