Basic Science Departments | College of Medicine

Primary Faculty

Darrin Akins, PhD

Darrin Akins, PhD

Professor, Associate Vice President for Health Sciences Research

Education:

Ph.D.: 1995, University of Texas Southwestern Medical Center, Dallas

Pre-OUHSC:

University of Texas Southwestern Medical Center, Dallas

Research Interests:

Pathogenic spirochetes, Lyme disease pathogenesis, host-parasite relationships.

Teaching:

Molecular Microbiology, Microbial Pathogenesis

Contact Information:

Office: BMSB 1005

Email: Darrin-Akins@ouhsc.edu 

Research Interests:

Lyme disease (Lyme borreliosis), a multisystem disorder characterized by dermatologic, cardiac, neurologic, and rheumatologic manifestations, is the most common tick-borne infection in the United States. The spirochetal agent of Lyme disease, Borrelia burgdorferi, is maintained in nature through a complex enzootic cycle which typically involves wild rodents and ticks of the genus Ixodes.

 

To maintain this cycle in nature, B. burgdorferi physiologically adapts to two dramatically different environments. Interestingly, recent studies have indicated that several borrelial antigens are expressed specifically in either the tick or mammalian host environment. Furthermore, there is now a substantial body of evidence indicating that B. burgdorferi dramatically alters its antigenic composition during tick-feeding and subsequent to host transmission.

 

In fact, the term "host-adapted" has been coined to describe the phenotype of this spirochete as it appears in the mammalian host during a natural infection. The antigenic changes which occur during mammalian infection are thought to play a key role in this organisms ability to persist for long periods of time in an infected host despite the robust humoral and cellular immune responses it elicits. Therefore, a major focus of our laboratory is to identify antigens expressed exclusively in the mammalian host environment and determine their potential role in immunoevasion and host-parasite interactions during infection.

 

B. burgdorferi has a rather unusual genetic organization for a prokaryotic organism. It contains a linear chromosome and numerous circular and linear plasmids. Interestingly, almost all of the differentially expressed borrelial antigens identified to date have been localized to plasmid elements. Given that B. burgdorferi virulence has been correlated with its plasmid content, we are investigating the role of plasmid-encoded proteins in Lyme disease pathogenesis.

 

Presently, we are focusing these research efforts on a group of previously identified circular plasmid-encoded proteins which are differentially expressed in either the tick or mammalian environment. A unique phylogenetic trait of these proteins is that although they comprise three unrelated groups, they all share an almost identical export signal with each other and with other borrelial outer surface proteins. It appears that all three families are the result of gene fusion events which brought together distinct proteins with a single export signal.

 

We are presently investigating the implications of this evolutionarily unstable group of proteins and are using them as a model system to better understand differential gene expression and host-adaptation in B. burgdorferi. At the same time, we also are determining the potential utility of these proteins as novel serodiagnostic tools and vaccine candidates for Lyme disease.

 

Lastly, a recently developed animal model now allows us to generate large numbers of mammalian host-adapted spirochetes for further molecular studies. We are utilizing this novel animal model in conjunction with several differentially expressed, plasmid-encoded proteins to help elucidate the signal(s) that result in B. burgdorferi "switching" to the host-adapted phenotype. The overall goal of this research is to gain a better understanding of the dynamics of the host-adaptation process which appears to be an important part of the parasitic strategy of the Lyme disease spirochete.

 

Changes in the polypeptide profile of "mammalian host-adapted" B. burgdorferi  

Comparison of the polypeptide profiles of B. burgdorferi grown in vitro at 23° C, 34° C, or temperature-shifted to 37° C, and host-adapted (HA)B. burgdorferi cultivated in rat peritoneal chambers. Asterisks indicate polypeptides which are downregulated or "turned off" when compared with the HA polypeptide profile. Arrows in the HA lane indicate newly expressed or upregulated polypeptides seen only in "mammalian host-adapted" B. burgdorferi.  

 

Current Lab Personnel:

Melisha Kenedy, Ph.D., Assistant Professor of Research

Natalie Sullivan, MS, Sr. Staff Research Assistant

Kari Hall, Graduate Research Assistant

Hannah Bowen, Graduate Research Assistant

Selected Publications:

A full list of publications can be found here.



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