Annotated Bibliography

Bechelli, Jeremy R., Elena Rydkina, Punsiri M. Colonne, and Sanjeev K. Sahni. 2009. “Rickettsia Rickettsii Infection Protects Human Microvascular Endothelial Cells against Staurosporine-Induced Apoptosis by a cIAP2-Independent Mechanism.” Journal of Infectious Diseases 199 (9): 1389–98. doi:10.1086/597805.

  • This paper examines the connection between Rickettsia rickettsii infection and resistance to apoptosis. This study attempts to find a link between the bacteria regulating cell death that would result from staurosporine being introduced to the cells by the clAP2-independent mechanism. The study could not conclude that the infection reduced apoptosis, even though there was upregulation of clAP2 after infection, because there must be more complex mechanisms acting as well.

Chan, Yvonne G. Y., Marissa M. Cardwell, Timothy M. Hermanas, Tsuneo Uchiyama, and Juan J. Martinez. 2009. “Rickettsial Outer-Membrane Protein B (rOmpB) Mediates Bacterial Invasion through Ku70 in an Actin, c-Cbl, Clathrin and Caveolin 2-Dependent Manner.” Cellular Microbiology 11 (4): 629–44. doi:10.1111/j.1462-5822.2008.01279.x

  • This paper is helpful for understanding the mechanism of how the bacteria is able to invade host cells.

Choi, Edwin, Natasha J. Pyzocha, and Douglas M. Maurer. 2016. “Tick-Borne Illnesses.” Current Sports Medicine Reports 15 (2): 98–104. doi:10.1249/JSR.0000000000000238.

  • This paper gives information on a variety of tick-borne illnesses, as well as useful information for being able to distinguish Rock Mountain Spotted fever from other diseases based on their presentation in different regions.

Dantas-Torres, Filipe. 2007. “Rocky Mountain Spotted Fever.” The Lancet Infectious Diseases 7 (11): 724–32. doi:10.1016/S1473-3099(07)70261-X.

  • This paper gives a good summary of a lot of the history of Rocky Mountain Spotted Fever and its tick vector. It also gives a lot of information on the disease itself such as prevalence, epidemiology, symptoms, transmission, diagnosis and treatment.

Denison, Amy M., Bijal D. Amin, William L. Nicholson, and Christopher D. Paddock. 2014. “Detection of Rickettsia Rickettsii, Rickettsia Parkeri, and Rickettsia Akari in Skin Biopsy Specimens Using a Multiplex Real-Time Polymerase Chain Reaction Assay.” Clinical Infectious Diseases 59 (5): 635–42.

  • This paper shows how the bacteria was isolated from infected skin cells in order to find better ways to study the disease. It provides interesting information by isolating the bacteria by literally taking pieces of the phenotypic symptoms (skin rash) of Rocky Mountain spotted fever.

Doxycycline – FDA Prescribing Information, Side Effects and Uses.” 2016. Accessed May 7. http://www.drugs.com/pro/doxycycline.html.

  • This website describes the mechanism of Doxycycline as well as provides a lot of general information on the drug itself.

Dzul-Rosado, K., G. Peniche-Lara, R. Tello-Martín, J. Zavala-Velázquez, R. de Campos Pacheco, M. B. Labruna, E. C. Sánchez, and J. Zavala-Castro. 2016. “Rickettsia Rickettsii Isolation from Naturally Infected Amblyomma Parvum Ticks by Centrifugation in a 24-Well Culture Plate Technique.” Open Veterinary Journal 3 (2): 101–5.

  • This paper shows a study where Ricketsia rickettsiiwas isolated from infected tick eggs. It provides helpful information on the exact isolation methods, including types of PCR and primers, to be able to study the bacteria in the most efficient way possible

Felsheim, Roderick F., Timothy J. Kurtti, and Ulrike G. Munderloh. 2009. “Genome Sequence of the Endosymbiont Rickettsia Peacockii and Comparison with Virulent Rickettsia Rickettsii: Identification of Virulence Factors.” PLoS ONE 4 (12): 1–10. doi:10.1371/journal.pone.0008361.

  • This paper gives a comparison of the genome sequences of two different Rickettsia strains, one non-pathogenic and one virulent, in order to determine the differences that could cause the Rickettsia peacockiito no longer be infectious. The mutations and deletions from the Rickettsia rickettsii in the non-pathogenic form were identified by the sequence comparison as well.

Gong, Wenping, Pengcheng Wang, Xiaolu Xiong, Jun Jiao, Xiaomei Yang, and Bohai Wen. 2015. “Chloroform-Methanol Residue of Coxiella Burnetii Markedly Potentiated the Specific Immunoprotection Elicited by a Recombinant Protein Fragment rOmpB-4 Derived from Outer Membrane Protein B of Rickettsia Rickettsii in C3H/HeN Mice.” PLoS ONE 10 (4): 1–18. doi:10.1371/journal.pone.0124664.

  • This paper studies the effect of treating infected mice with rOmpB-4 and chloroform-methanol residue in an attempt to increase immunity of the infected species. The results show that treatment with the two conditions together could have a significant effect on protection from Rickettsia rickettsii.

Gong, Wenping, Pengcheng Wang, Xiaolu Xiong, Jun Jiao, Xiaomei Yang, and Bohai Wen. 2015. “Enhanced Protection against Rickettsia Rickettsii Infection in C3H/HeN Mice by Immunization with a Combination of a Recombinant Adhesin rAdr2 and a Protein Fragment rOmpB-4 Derived from Outer Membrane Protein B.” Vaccine 33 (8): 985–92. doi:10.1016/j.vaccine.2015.01.017.

  • This paper focuses on attempts to increase immunoprotection against infection by Rickettsia rickettsii in mice through testing two specific surface proteins of the bacteria determined to be protective antigens, OmpB and Adr2. The combination of immunizing both proteins together showed significantly more protection against the disease than by isolating one of them alone in host cells.

Gong, Wenping, Xiaolu Xiong, Yong Qi, Jun Jiao, Changsong Duan, and Bohai Wen. 2014. “Identification of Novel Surface-Exposed Proteins of Rickettsia Rickettsii by Affinity Purification and Proteomics.” PLoS ONE 9 (6): 1–10. doi:10.1371/journal.pone.0100253.

  • This paper gives information on which surface proteins of the Rickettsia rickettsiaare used for transmission into hosts. The study shows isolation of these proteins through various methods like affinity purification and electrophoresis in order express the proteins in  coli cells for further study of which host cells are affected in mice after infection.

Levin, Michael L., Lindsay F. Killmaster, Galina E. Zemtsova, Jana M. Ritter, and Gregory Langham. 2014. “Clinical Presentation, Convalescence, and Relapse of Rocky Mountain Spotted Fever in Dogs Experimentally Infected via Tick Bite.” PloS One 9 (12): e115105. doi:10.1371/journal.pone.0115105.

  • This paper examines Rocky Mountain spotted fever in dogs after transmission from infected ticks rather than many previous studies that infected animals from cultures of Rickettsia rickettsii. The purpose was to examine full life cycle to develop best possible analysis and treatment of the disease.

Martinez, Juan J., and Pascale Cossart. 2004. “Early Signaling Events Involved in the Entry of Rickettsia Conorii into Mammalian Cells.” Journal of Cell Science 117 (Pt 21): 5097–5106. doi:10.1242/jcs.01382.

  • This paper provides an accurate summary of cellular events that lead to the incorporation of rickettsia species into host cells.

Martinez, Juan J., Stéphanie Seveau, Esteban Veiga, Shigemi Matsuyama, and Pascale Cossart. 2005. “Ku70, a Component of DNA-Dependent Protein Kinase, Is a Mammalian Receptor for Rickettsia Conorii.” Cell 123 (6): 1013–23. doi:10.1016/j.cell.2005.08.046.

  • This is the landmark paper that establishes Ku70 as the necessary receptor for rickettsia to bind and be able to be incorporated into the cell.

Noriea, Nicholas F., Tina R. Clark, and Ted Hackstadt. 2015. “Targeted Knockout of the Rickettsia Rickettsii OmpA Surface Antigen Does Not Diminish Virulence in a Mammalian Model System.” mBio 6 (2): e00323–15. doi:10.1128/mBio.00323-15.

  • This paper shows a contrast to many other studies because it shows that knockout of OmpA did not decrease the virulence of the bacteria. This is significant because it shows that OmpA is not necessary in the bacteria for virulence. This study attempted to open the doors to new research for Rocky Mountain spotted fever by looking for other determinants of infection.

Policastro, Paul F., and Ted Hackstadt. 1994. “Differential Activity of Rickettsia Rickettsii ompA and ompB Promoter Regions in a Heterologous Reporter Gene System.” Microbiology (13500872) 140 (11): 2941.

  • This paper attempts to examine why the OmpB promoter region rather than the OmpA is selectively favored for insertion. Both outer membrane proteins are large antigens located on the surface of Rickettsia rickettsii.

Purvis, J. J., and M. S. Edwards. 2000. “Doxycycline Use for Rickettsial Disease in Pediatric Patients.” The Pediatric Infectious Disease Journal 19 (9): 871–74.

  • This paper examines the effect of antibiotic treatment for rickettsial disease in children and gives areas where treatment for Rocky Mountain spotted fever could potentially be improved.

Raghavan, Ram K., Douglas G. Goodin, Daniel Neises, Gary A. Anderson, and Roman R. Ganta. 2016. “Hierarchical Bayesian Spatio-Temporal Analysis of Climatic and Socio-Economic Determinants of Rocky Mountain Spotted Fever.” PloS One 11 (3): e0150180. doi:10.1371/journal.pone.0150180.

  • This paper examines the effects of environmental and climatic changes on Rocky Mountain spotted fever in terms of incidence and other factors associated with the disease. It also examines the spread of the disease in terms of socio-economic status of individuals.

Ricketts H. T. 1906a. “The Study of ‘Rocky Mountain Spotted Fever’ (tick Fever?) by Means of Animal Inoculations.a Preliminary Communication.” Journal of the American Medical Association XLVII (1): 33–36. doi:10.1001/jama.1906.25210010033001j.

  • This is a preliminary paper that studied Rocky Mountain spotted fever in an attempt to figure out the vector of the disease.

Ricketts H. T. 1906b. “The Transmission of Rocky Mountain Spotted Fever by the Bite of the Wood-Tick (dermacentor Occidentalis).” Journal of the American Medical Association XLVII (5): 358–358. doi:10.1001/jama.1906.25210050042002j.

  • This is a paper that shows rickettsia is able to be transferred to hosts via the bite of a tick. It is a continuation of the above paper.

Ricketts H. T. 1907. “The Role of the Wood-Tick (dermacentor Occidentalis) in Rocky Mountain Spotted Fever,and the Susceptibility of Local Animals to This Disease—a Preliminary Report.” Journal of the American Medical Association XLIX (1): 24–27. doi:10.1001/jama.1907.25320010024002g.

  • This is the landmark paper that fully establishes the specific tick as the vector for Rocky Mountain spotted fever for the first time in history.

Ricketts H. T. 1909. “A Micro-Organism Which Apparently Has a Specific Relationship to Rocky Mountain Spotted Fever: A Preliminary Report.” Journal of the American Medical Association LII (5): 379–80. doi:10.1001/jama.1909.25420310039002.

  • This paper is a continuation of the above landmark paper and it establishes that a microorganism is responsible for the infection, and that it is present in both the host and the vector.

Riley, Sean P., Marissa M. Cardwell, Yvonne G. Y. Chan, Ludovic Pruneau, Fabio Del Piero, and Juan J. Martinez. 2015. “Failure of a Heterologous Recombinant Sca5/OmpB Protein-Based Vaccine to Elicit Effective Protective Immunity against Rickettsia Rickettsii Infections in C3H/HeN Mice.” Pathogens and Disease 73 (9): ftv101. doi:10.1093/femspd/ftv101.

  • This paper shows the failed attempt to vaccinate against Rocky Mountain spotted fever by using recombinant OmpB as the antigen to create immunity against the bacteria. The study shows the fact that it is not the best vaccine to create immunity to the disease, which means that other strategies should be looked into to try and develop a more effective immunity-producing strategy.

Rydkina, Elena, David J. Silverman, and Sanjeev K. Sahni. 2005. “Activation of p38 Stress-Activated Protein Kinase during Rickettsia Rickettsii Infection of Human Endothelial Cells: Role in the Induction of Chemokine Response.” Cellular Microbiology 7 (10): 1519–30. doi:10.1111/j.1462-5822.2005.00574.x.

  • This paper identified a connection between infection of endothelial cells with Rickettsia rickettsii and activation of p38, which plays a role in inflammation response. The study showed that p38 was activated, which allowed the researchers to question possibilities of inhibiting p38 as a response to limit more adverse symptoms of Rocky Mountain spotted fever therapeutically.

Rydkina, E., L. C. Turpin, D. J. Silverman, and S. K. Sahni. 2009. “Rickettsia Rickettsii Infection of Human Pulmonary Microvascular Endothelial Cells: Modulation of Cyclooxygenase-2 Expression.” Clinical Microbiology & Infection 15 (December): 300–302. doi:10.1111/j.1469-0691.2008.02247.x.

  • This paper examines the effect on cyclooxygenase-2 as a result of human pulmonary microvascular endothelial cell infection by the bacteria. The study uncovers another link where the disease modulates host cell defenses in order for the bacteria to survive longer.

Saraiva, Danilo G., Herbert S. Soares, João Fábio Soares, and Marcelo B. Labruna. 2014. “Feeding Period Required by Amblyomma Aureolatum Ticks for Transmission of Rickettsia Rickettsii to Vertebrate Hosts.” Emerging Infectious Diseases 20 (9): 1504–10. doi:10.3201/eid2009.140189.

  • This paper gives information about the feeding period and attachment time necessary for ticks to be able to transmit the bacterium to hosts.

Symptoms, Diagnosis, and Treatment | Rocky Mountain Spotted Fever (RMSF) | CDC.” 2016. Accessed May 6. http://www.cdc.gov/rmsf/symptoms/.

  • This website gives a lot of general information about Rocky Mountain spotted fever including treatment and symptoms of the disease.

Walker, David H., and Nahed Ismail. 2008. “Emerging and Re-Emerging Rickettsioses: Endothelial Cell Infection and Early Disease Events.” Nature Reviews Microbiology 6 (5): 375–86. doi:10.1038/nrmicro1866.

  • This paper provides an overview of various aspects of Rocky Mountain spotted fever. It gives a good understanding of pathogenesis, infection of host cells and mechanisms, and mechanisms of host cell response.