While there have been a lot of studies done in the past to attempt elucidate the mechanism of infection of Rocky Mountain spotted fever there is still a lot of work that needs to be done. Additionally, the scientific literature seems to be lacking in treatment methods due to the fact that Doxycycline has really been the only antibiotic to positively treat infected patients with significant results. After thoroughly investigating Rocky Mountain spotted fever from a variety of angles, it is clear that there are definitely places where future studies need to be done to uncover more about the disease and its bacterial pathogen.
In the current literature, there are many studies shown uncovering new surface proteins that play a role in binding of rickettsia to target host cells; however, most of these studies conclude by stating that although there are other proteins involved, the exact function is unknown (Gong et al 2014). The fact that there are so many proteins covering the surface of these bacterial species makes it very difficult to understand exactly how R. rickettsii is able to enter endothelial cells. Studies similar to the one mentioned above that uncovered five novel surface proteins, need to be examined from a different view point to understand the exact interactions between receptors and ligands of rickettsia infection. OmpB is essentially the only target of research for the mechanism of binding to endothelial cells by the bacteria, and even this interaction is not that well known. The scientists studying the surface proteins of R. rickettsii should attempt to compare the bacterial surface proteins that are known to be involved in binding with proteins present already in the human body that bind to similar receptors based on structure. Because of the fact that little is known about the bacterial surface protein interactions apart from OmpB, a lot of studies have only attempted to create vaccines using a recombinant form of OmpB (Gong et al. 2015). If more information were obtained about the other proteins, it is possible that another protein could be necessary for bacterial invasion that has not been seen before. This new protein could potentially be a drug that inhibits binding of R. rickettsii to human cells so that the bacteria are unable to enter cells and replicate in the first place.
Even more so than the fact that more research needs to be done on the surface proteins on rickettsia species, the mechanism of exactly how the bacteria is able to enter endothelial cells needs to be elucidated much more. Although the mechanism of how R. rickettsii infects host endothelial cells is generally shown in the literature, there are many pieces of it that could benefit from future research. Even though there are crystal structures of bacterial OmpB and the receptor to which it binds, Ku70, it is disconcerting that the exact way rickettsia species interact and enter the cells here is still unclear. Studies done by Martinez et al. even attempt to describe the mechanism by which the OmpB-Ku70 complex facilitates the invasion of R. rickettsii into the cell, but show that the exact path is unclear. A possible way to investigate this problem could be through a series of tests, such as cross-linking and/or pull-down assays, that could isolate OmpB and Ku70 so their interactions could be studied. If more information could be obtained about the exact structural interactions between both rickettsia and human surface cells, it is possible that a drug could be created to inhibit this binding without altering the expression of Ku70 and its role in healthy cell function.
Another area of study that could benefit from future research is the use preventative measures prior to infection with R. rickettsii and prior to bite of infected tick. While there have been studies done on the feeding period required for transmission of R. rickettsii from vector to host (Saraiva et al. 2014), there is no significant research available on how to prevent the tick from staying attached in the first place. While any generic bug spray product may prevent ticks from coming into contact with the shielded skin, it is not possible to consider this viable protection. It would not only be too inconvenient to put on bug spray every day, but also the current products available on the market are not 100 percent effective. Future research could potentially be done to consider a drug administered that would prevent ticks from staying attached long enough to transfer the infective agent. It would be interesting to see if a drug has the potential to be toxic for ticks but still able to circulate in our body. The possibility of a chemical manifesting itself in our skin cells that would be released upon puncture of the skin by tick bite, which would in turn either kill the tick or simply cause it to detach itself from the host is something that is very intriguing.