Posted February 14, 2024

Rebecca Lamason, Ph.D., Massachusetts Institute of Technology

Tick bites can cause life-threatening or chronic illnesses. Many of the diseases transmitted by tick bite are the result of infection by harmful bacteria that reside within the mouthparts of the tick. These bacteria are obligate intracellular, which means they rely on arthropod and vertebrate hosts for survival, including their reproduction and spread to other hosts.

The Spotted Fever Group Rickettsia are one group of obligate intracellular bacteria that use tick-host interactions to support their survival. Upon infection via tick bite, SFG Rickettsia can cause Rocky Mountain spotted fever and Pacific Coast tick fever – vascular diseases that can be life-threatening or even fatal. RMSF is difficult to treat, and mortality rates can be as high as 20%-30%.¹ These treatment challenges are rooted in a lack of understanding of how the bacteria complete their multistep life cycle and infect host cells.

With a fiscal year 2020 Tick-Borne Disease Research Program Idea Development Award, Rebecca Lamason, Ph.D., and her team at the Massachusetts Institute of Technology aimed to identify how SFG Rickettsia invade and survive within host cells. Many pathogenic bacteria successfully occupy the cell by secreting effector proteins that can reprogram the host cell to their advantage and allow for the use of important host nutrients for growth.² It is a challenge to study the potential effects and targets of SFG Rickettsia’s dependence on the host because these obligate intracellular bacteria are difficult to grow in the laboratory. Dr. Lamason’s lab found a way to overcome these challenges.

Using the rickettsia species R. parkeri as a model, Lamason and her team began to uncover potential effector proteins. According to the research team, they are the first team on record to adapt a preexisting biochemical protein-labeling tool, BONCAT, for use in obligate intracellular bacterium. The team generated a strain of R. parkeri capable of expressing MetRS, a protein biosynthesis enzyme. The creation of this MetRS expressing strain of R. parkeri was necessary for BONCAT to identify rickettsia-specific proteins. After ensuring BONCAT could successfully label bacteria that expressed MetRS, the team infected host cells with the MetRS strain of bacteria.

The research conducted by Dr. Lamason’s lab under this TBDRP Idea Development Award, including the identification of novel rickettsia effector proteins, increased the understanding of rickettsia pathogenesis. The biochemical gene-targeting tools created by Lamason and her team established a basis for research on other rickettsia species and expanded the understanding of tick-mediated transmission. As rates of rickettsia-linked disease increase and threaten Service Members and the public, according to Dr. Lamason the findings from this CDMRP-funded research have the potential to reveal targets for therapeutic development. Additionally, one of the effector proteins identified by this research, SrfA, has potential as a diagnostic tool to aid in early detection and proper diagnosis of rickettsial diseases.

References:

¹Snowden J and Simonsen KA. 2023. Rocky Mountain Spotted Fever (Rickettsia rickettsii). [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. https://www.ncbi.nlm.nih.gov/books/NBK430881/

²Helminiak, L., Mishra, S., & Kim, H. K. (2022). Pathogenicity and virulence of Rickettsia. Virulence, 13(1), 1752–1771. https://doi.org/10.1080/21505594.2022.2132047

Link:
Public and Technical Abstracts: Elucidating the Mechanisms of Spotted Fever Group Rickettsia Pathogenesis

Top of Page