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Jon S. Blevins, Ph.D.
Assistant Professor, Department of Microbiology & Immunology Research Interest: Pathogenesis of the Lyme disease spirochete, Borrelia burgdorferi Ph.D.: University of Arkansas for Medical Sciences, Little Rock, AR Postdoctoral: University of Texas Southwestern Medical Center, Dallas, TX Phone: (501) 296-1253 Research Description Lyme disease, caused by the spirochetal bacterium Borrelia burgdorferi, is the most prevalent arthropod-borne disease in the United States and Europe. Although early stage Lyme disease often can be treated with antibiotics, if left untreated, the disease can progress to become a devastating chronic illness, most frequently characterized by heart block, peripheral neuropathies, and migratory arthritis. Although it has been over 20 years since B. burgdorferi was first isolated, there is still much progress to be made towards understanding the contributions of B. burgdorferi's individual genes to issues of tick colonization (maintenance in the environment), mammalian infectivity (ability to infect human skin), and pathogenicity (tissue dissemination and chronic infection). The zoonotic life cycle of B. burgdorferi is complex, involving both an arthropod tick (Ixodes scapularis) vector and a mammalian host. The ability of B. burgdorferi to occupy these two very diverse niches is governed by a complex regulatory shift that dramatically alters the expression of several major outer surface proteins. One of the most important findings in the area of B. burgdorferi pathogenesis research was the identification of the Rrp2/RpoN/RpoS alternative sigma factor cascade. Mutational experiments have confirmed that this regulatory network is required for the aforementioned regulatory shift and vital for both vector-to-host transmission and establishing an infection in the mammal. Although subsequent experimentation has identified several Rrp2/RpoN/RpoS-regulated major outer surface lipoproteins (e.g. OspC and DbpA) that are partially responsible for the attenuated pathogenic phenotype exhibited by the B. burgdorferi mutant lacking this regulatory network, transcriptional microarray analyses carried out on this same mutant strain indicate that the impact of the Rrp2/RpoN/RpoS regulatory pathway extends far beyond just these two outer surface proteins. Therefore, additional work is required identify and characterize other genes within this regulon that might potentially play a role in the infectious life cycle of B. burgdorferi. Given that B. burgdorferi has been exceedingly refractory to methods typically used to genetically manipulate other bacteria, the need for new genetic approaches for manipulation, regulatory studies, and mutational analysis are paramount. To this end, significant emphasis has been placed on developing new techniques for the genetic analysis and genetic manipulation of the spirochete. I have successfully adapted a controllable/inducible gene expression system, which expresses a desired gene in a switch-like manner, and a new gene expression reporter for studying gene regulation in the Lyme disease spirochete. Application of these two systems should help garner new information about how virulence expression is regulated in B. burgdorferi and, ultimately, help to break open studies on many aspects of Lyme disease pathogenesis and chronicity.References Blevins J.S., Xu, H., He, M., Norgard, M.V., Reitzer, L., and Yang, X.F. 2009. Rrp2, a sigma54-dependent transcriptional activator of Borrelia burgdorferi, activates rpoS in an enhancer-independent manner. J. Bacteriol . 191:2902-2905. Blevins, J.S., Doty, A., Limke, T., and Montalto, J.G. 2009. Identification of a source of bovine serum albumin that consistently supports Borrelia burgdorferi cultivation and differential expression. BioProcess Intl. 7: 26-34. He, M., Oman, T., Xu, H., Blevins J., Norgard, M.V., and Yang, X.F. 2008. Abrogation of ospAB constitutively activates the Rrp2-RpoN-RpoS pathway (sigmaN-sigmaS cascade) in Borrelia burgdorferi. Mol. Microbiol. 70 :1453-1464. Yang, X.F., Goldberg, M.S., He, M., Xu, H., Blevins, J.S., and Norgard M.V. 2008. Differential expression of a putative CarD-like transcriptional regulator, LtpA, in Borrelia burgdorferi. Infect. Immun.76:4439-4444. Ouyang, Z., Blevins, J.S. (co-first author) and Norgard, M.V. 2008. Transcriptional interplay among the regulators Rrp2, RpoN and RpoS in Borrelia burgdorferi. Microbiology. 154:2641-2658. Blevins, J.S., Hagman, K.E., and Norgard, M.V. 2008. Assessment of decorin-binding protein A to the infectivity of Borrelia burgdorferi in the murine models of needle and tick infection. BMC Microbiol. 8:82. Machius, M., Brautigam, C.A., Tomchick, D.R., Ward, P., Otwinowski, Z., Blevins, J.S., Deka, R.K., and Norgard, M.V. 2007. Structural and biochemical basis for polyamine binding to the Tp0655 lipoprotein of Treponema pallidum : putative role of Tp0655 (TpPotD) as a polyamine receptor. J. Mol. Biol. 373:681-694. Blevins, J.S., Revel, A.T., Smith, A.H., Bachlani, G.N., and Norgard, M.V. 2007. Adaptation of a luciferase gene reporter and lac expression system to Borrelia burgdorferi. Appl. Environ. Microbiol .73:1501-1513. Smith, A.H., Blevins, J.S., Bachlani, G.N., Yang, X.Y., and Norgard, M.V. 2007. Evidence that RpoS (sigma S) in Borrelia burgdorferi is controlled directly by RpoN (sigma 54/sigma N). J. Bacteriol. 189:2139-2144. Deka, R.K., Brautigam, C.A., Yang, X.F., Blevins, J.S., Machius, M., Tomchick, D.R., and Norgard, M.V. 2006. The PnrA (Tp0319; TmpC) lipoprotein represents a new family of bacterial purine nucleoside receptor encoded within an ATP-binding cassette (ABC)-like operon in Treponema pallidum. J. Biol. Chem. 281:8072-8081. Yang, X., Lybecker, M.C., Pal, U., Alani, S.M., Blevins, J., Revel A.T., Samuels, D.S., and Norgard, M.V. 2005. Analysis of the ospC regulatory element controlled by the Rrp2-RpoN-RpoS regulatory pathway in Borrelia burgdorferi. J. Bacteriol. 187:4822-4829. Revel, A.T., Blevins, J.S. (co-first author), Almazán, C., de la Fuente, J., Hagman, K.E., and Norgard, M.V. 2005. bptA (bbe16) is essential for the persistence of the Lyme disease spirochete, Borrelia burgdorferi, in its natural tick vector. Proc. Natl Acad. Sci. U.S.A. 102:6972-6977. O'Leary, J.O., Langevin, M.J., Price, C.T.D., Blevins, J.S. , Smeltzer, M.S., and Gustafson, J.E. 2004. Effects of sarA inactivation on intrinsic multi-antibacterial resistance of Staphylococcus aureus. FEMS Microbiol. Let. 237 297-302. Blevins, J.S., Revel, A.T., Caimano, M.J., Yang, X.F., Richardson, J.A., Hagman, K.E., and Norgard, M.V. 2004. The luxS gene is not required for Borrelia burgdorferi tick colonization, transmission to a mammalian host, or induction of disease. Infect. Immun. 72 :4864-4867. Beenken, K.E., Dunman, P.M., McAleese, F., Macapagal, D., Murphy, E., Projan, S.J., Blevins, J.S., and Smeltzer, M.S. 2004. Global gene expression in Staphylococcus aureus biofilms. J. Bacteriol. 186:4665-4684. Sterba, K.M., Mackintosh, S.G., Blevins, J.S., Hurlburt, B.K., and Smeltzer, M.S. 2003. Characterization of Staphylococcus aureus SarA binding sites. J. Bacteriol. 185:4410-4417. Beenken, K.E., Blevins, J.S., and Smeltzer, M.S. 2003. Mutation of sarA in Staphylococcus aureus limits biofilm formation. Infect. Immun. 71:4206-4211. Blevins, J.S., Elasri, M.O., Allmendinger, S.A., Beenken, K.E., Skinner, R.A., Thomas, J.R., and Smeltzer, M.S. 2003. Role of sarA in the pathogenesis of Staphylococcus aureus musculoskeletal infection. Infect. Immun. 71:516-523. Blevins, J.S., Beenken, K.E., Elasri, M.O. Hurlburt, B.K. and Smeltzer, M.S. 2002. Strain-dependent differences in the regulatory roles of sarA and agr in Staphylococcus aureus. Infect. Immun. 70:470-480. Elasri, M.O., Thomas, J.R., Skinner, R.A., Blevins, J.S., Beenken, K.E., Nelson, C.L. and Smeltzer, M.S. 2002. Staphylococcus aureus collagen adhesin contributes to the pathogenesis of osteomyelitis. Bone. 30:275-280. Mason, W.J., Blevins, J.S., Beenken, K.E., Gardner, M.R., Wibowo, N., Ojha, N. and Smeltzer, M.S. 2001. Multiplex PCR protocol for the diagnosis of staphylococcal infection. J. Clin. Micro. 39:3332-3338. Blevins, J.S., Gillaspy, A.F., Rechtin, T.M., Hurlburt, B.K. and Smeltzer, M.S. 1999. The staphylococcal accessory regulator (sar) represses transcription of the Staphylococcus aureus collagen adhesin gene (cna) in an agr-independent manner. Mol. Microbiol. 33:317-326.
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