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Chris Elkins
Contact Information: Division of Microbiology Phone: (870) 543-7547 Education: Dr. Elkins received a Bachelor of Arts degree in Biology and History at Case Western Reserve University in 1994 and a Ph.D. degree in Microbiology from the University of Tennessee, Knoxville in 2001 under the mentorship of Dr. Dwayne C. Savage. He subsequently was appointed as postdoctoral fellow in the Department of Molecular and Cell Biology at the University of California at Berkeley in the laboratory of Dr. Hiroshi Nikaido. He joined the Food and Drug Administration, National Center for Toxicological Research (NCTR), in January of 2003 as a principal investigator in the Division of Microbiology. Research Interest: My research interests address antibiotic resistance mechanisms with a focus on microbial transport systems and membrane permeability. Active drug transport (as with multidrug efflux pumps) provides intrinsic resistance to a wide array of important substrates (drugs, biocides, synthetic and natural detergents, and organic dyes and solvents) and are currently the subject of intense pharmaceutical and academic study to develop clinically successful inhibitors that could render microbial pathogens susceptible to a broad range of older antibiotics. Purely basic pursuits into efflux-mediated transport mechanisms are of interest, particularly tripartite gram-negative multiple drug resistance systems (i.e. Escherichia coli AcrAB-TolC, EmrAB-TolC) and their physiological role in the human-microbial ecology. They effectively transport a variety of natural steroid compounds, including bile acids and hormones, and supply qualitatively and quantitatively the largest degree of active intrinsic drug resistance of, quite possibly, any single genetically-encoded factor. Research Description: My research is also approached from the host gastrointestinal and vaginal environments with investigations into antibiotic resistance development of commensal microbes and microbes used in probiotic therapy. Of particular importance are the lactobacilli and the capacity for these organisms to exert probiotic benefits and serve as indicators of GI and vaginal tract health. Thus as an alternative to classical antibiotic therapy, live supplements of innocuous commensal microbes may attenuate infection potential caused by transient pathogens and associated disease development. As such, factors that contribute to their maintenance in these niches or, alternatively, their exclusion of potentially pathogenic organisms are currently under investigation. The issue of drug resistance is tangentially related to our understanding of commensal maintenance since these organisms are exposed to every drug therapy ingested intentionally or otherwise by the host. It is fundamentally interesting to identify the impact that certain drugs have on the commensal microbiota under conditions reflected in these environments that contain, for instance, high concentrations of natural antimicrobial steroid compounds like bile acids. In a somewhat converse situation, gram-positive membrane permeability is probably a stronger contributing factor than efflux to potential resistance phenotypes. Because of this characteristic and with regards to vaginal tract Lactobacillus, resistances to lipophilic topical agents, microbicides, spermicides, lubricants, etc. may impact the predominance of Lactobacillus in this region and the potential for developing vaginosis and/or drug cross-resistance. Publications 1. Elkins, C.A., and D.C. Savage. 1998. Identification of genes encoding conjugated bile salt hydrolase and transport in Lactobacillus johnsonii 100-100. J. Bacteriol. 180:4344-4349. 2. Elkins, C.A., S.A. Moser, and D.C. Savage. 2001. Genes encoding bile salt hydrolases and conjugated bile salt transporters in Lactobacillus johnsonii 100-100 and other Lactobacillus species. Microbiology. 147:3403-3412. 3. Elkins, C.A., and H. Nikaido. 2002. Substrate specificity of the RND-type multidrug efflux pumps AcrB and AcrD of Escherichia coli is determined predominately by two large periplasmic loops. J. Bacteriol. 184:6490-6498. 4. Elkins, C.A., and H. Nikaido. 2003. 3D structure of AcrB: the archetypal multidrug efflux transporter of Escherichia coli likely captures substrates from periplasm. Drug Res. Updates. 6:9-13. 5. Elkins, C.A., and H. Nikaido. 2003. Chimeric analysis of AcrA function reveals the importance of its C-terminal domain in its interaction with the AcrB multidrug efflux pump. J. Bacteriol. 185:5349-5356. 6. Elkins, C.A.*, and D.C. Savage. 2004. CbsT2 from Lactobacillus johnsonii 100-100 is a transport protein of the major facilitator superfamily that facilitates bile acid antiport. J. Mol. Microbiol. Biotechnol. 6:76-87. 7. Elkins, C.A.*, and L.B. Mullis. 2004. Bile-mediated aminoglycoside sensitivity in Lactobacillus likely results from increased membrane permeability attributable to cholic acid. Appl. Environ. Microbiol. 70:7200-7209. 8. Elkins, C.A.* and K.E. Beenken. 2005. Modeling the tripartite drug efflux pump archetype: structural and functional studies of the macromolecular constituents reveal more than their names imply (Minireview, Lead Article). J. Chemother. 17:581-592. 9. Elkins, C.A.*, and L.B. Mullis. 2006. Mammalian steroid hormones are substrates for the major RND- and MFS-type tripartite multidrug efflux pumps of Escherichia coli. J. Bacteriol. 188:1191-1195. 10. Elkins, C.A.*, and L.B. Mullis. 2007. Substrate competition studies using whole cell accumulation assays with the major tripartite multidrug efflux pumps of Escherichia coli. Antimicrob. Agents Chemother. 51:923-929. 11. Elkins, C.A.*, M.E. Munoz, L.B. Mullis, and M.E. Hart. 2008. Lactobacillus-mediated inhibition of Staphylococcus aureus MN8, a menstrual toxic shock syndrome prototype, is unrelated to peroxide production. In submission. In Preparation Elkins, C.A.*, M.E. Muñoz, T. Han, L.B. Mullis, and J.C. Fuscoe. 2007. Transcriptomic response of Escherichia coli exposed to mammalian steroid hormones and their role in the host-commensal relationship. Dissertation Elkins, C.A. 2001. Molecular genetic analysis of bile salt hydrolase expression and transport in Lactobacillus johnsonii strain 100-100. Ph.D. dissertation. University of Tennessee, Knoxville.
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