Pamela L. C. Small

Professor Microbiology and Genome Sciences Technology University of Tennessee

Dr. Pamela Small is Professor of Microbiology at the University of Tennessee, Knoxville and a core faculty member in the Graduate Program in Genome Sciences Technology at Oak Ridge National Laboratory and University of Tennessee. Dr. Small grew up in the Midwest and completed three years of undergraduate work at the University of Wisconsin before moving to California where she obtained a B.A. in anthropology at California State University, Hayward in 1975. Dr. Small spent several years in India, from 1967-69 and 1974. During this time she developed an interest in infectious diseases and conducted research on local attitudes towards health and disease. In 1974 she published a book Banji Bene as a guide for foreign medical students at Manipal University Medical School, Manipal, Karnataka, India. Dr. Small obtained her Ph.D. from the Department of Microbiology and Immunology, Stanford University Medical School in 1982. After several years as assistant professor of microbiology at Middlebury College, Middlebury, Vermont, she accepted a position as head of a newly formed Facultative Intracellular Bacteria Unit at Rocky Mountain Laboratories, NIAID, NIH in Hamilton, MT. For the last six years she has been Professor of Microbiology at University of Tennessee.

Time spent in the tropics stimulated Dr. Small's interest in microbial pathogenesis along with a desire to conduct research in an area relevant to improving health conditions in resource poor countries. Her initial research focused on the genetics and cellular microbiology of virulence in intestinal pathogens (Shigella species). Since 1996 Dr. Small's research has focused on understanding the pathogenesis of the environmental pathogen Mycobacterium ulcerans, the causative agent of Buruli ulcer. The purification of a toxic macrolide, mycolactone from M. ulcerans' conducted in the Small laboratory laid the foundation for studies on the virulence and immunopathology of M. ulcerans. Identification of the mechanism and cellular target of this fascinating molecule is a major research interest for the Small lab. The Small lab has recently identified new mycolactones in M. liflandii, a pathogen of West African Clawed Frogs, in M. pseudoschottsii, a pathogen of striped bass in the Chesapeake Bay, and a unique clade M. marinum associated many fish species in the Red Sea. Dr. Small's interest in the evolution of virulence in these closely related pathogens has resulted in expanded research activities involving field and laboratory studies aimed at understanding the ecology of M. ulcerans. The goal of these studies is to identify areas where intervention strategies could be developed to prevent transmission of M. ulcerans from the environment to humans.

Dr. Small's research is supported by the National Institutes of Health, National Science Foundation, Optimus Foundation and the World Health Organization. She has published more than 60 articles in refereed journals including Journal of the American Chemical Society, Applied and Environmental Microbiology, Cellular Microbiology, Genome Research, Infection and Immunity, Molecular Microbiology, Proceedings of the National Academy of Sciences, Journal of Microbiology, and PLoS Neglected Tropical Diseases and Science as well as authored review articles and book chapters on the pathogenesis of Shigella, and Mycobacterial pathogens.

Dr. Small served as Division U Chair Mycobacteriology for the American Society of Microbiology and is currently an advisor. She is associate editor of PLoS Neglected Tropical Diseases, on the editorial board of Infection and Immunity, a member of the advisory board of the Faculty of 1000 Biology, and a member of the World Health Organization Technical Advisory Group for Buruli Ulcer.

Dr. Small teaches courses on Microbial pathogenesis and Global Health. She participates as a faculty member of Spetses Summer School on Microbial Pathogenesis and Survival in the Host and Environment.

Current Support

Ecology of Mycobacterium ulcerans infection: Evaluating Landscape Relationships with Freshwater Communitiees and Disease Occurrence. NSF/NIH Joint Grant (co-PI's M. Benbow, P. Small, J. Qi, and R.J. Stevenson) 2006-2011($1,999,986).

Transmission of Buruli Ulcer. Stop Buruli Consortium Optimus Foundation (co-PIs R.Merritt, Christian Johnson, Dorothy Yeboah-manu) 2008-2011 ($319,000)

Production of Mycolactone. World Health Organization, 2008-2009 ($12,000)

Publications on Mycobacterium ulcerans, mycolactone and Buruli ulcer

  1. Aubry S, Lee RE, Mahrous EA, Small PL, Beachboard D, Kishi Y. Synthesis and Structure of Mycolactone E Isolated from Frog Mycobacterium.Org Lett. 2008 Nov 1. [Epub ahead of print]
  2. Mosi L, Williamson H, Wallace JR, Merritt RW, Small PL. Persistent association of Mycobacterium ulcerans with the West African predaceous insect, Belostomatidae. Appl Environ Microbiol. 2008 Oct 3. [Epub ahead of print]
  3. Rybniker J, Plum G, Robinson N, Small PL, Hartmann P. Identification of three cytotoxic early proteins of mycobacteriophage L5 leading to growth inhibition in Mycobacterium smegmatis. Microbiology. 2008 Aug;154(Pt 8):2304-14.
  4. Wagner T, Benbow ME, Burns M, Johnson RC, Merritt RW, Qi J, Small PL. A Landscape-based model for predicting Mycobacterium ulcerans infection (Buruli Ulcer disease) presence in Benin, West Africa. Ecohealth. 2008 Mar;5(1):69-79. Epub 2008 Feb 8.
  5. Stinear TP, Seemann T, Harrison PF, Jenkin GA, Davies JK, Johnson PD, Abdellah Z, Arrowsmith C, Chillingworth T, Churcher C, Clarke K, Cronin A, Davis P, Goodhead I, Holroyd N, Jagels K, Lord A, Moule S, Mungall K, Norbertczak H, Quail MA, Rabbinowitsch E, Walker D, White B, Whitehead S, Small PL, Brosch R, Ramakrishnan L, Fischbach MA, Parkhill J, Cole ST. Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis. Genome Res. 2008 May;18(5):729-41. Epub 2008 Apr 10.
  6. Benbow ME, Williamson H, Kimbirauskas R, McIntosh MD, Kolar R, Quaye C, Akpabey F, Boakye D, Small P, Merritt RW. Aquatic invertebrates as unlikely vectors of Buruli ulcer disease. Emerg Infect Dis. 2008 Aug;14(8):1247-54.
  7. Williamson HR, Benbow ME, Nguyen KD, Beachboard DC, Kimbirauskas RK, McIntosh MD, Quaye C, Ampadu EO, Boakye D, Merritt RW, Small PL. Distribution of Mycobacterium ulcerans in Buruli Ulcer Endemic and Non-Endemic Aquatic Sites in Ghana. PLoS Negl Trop Dis. 2008 Mar 26;2(3):e205.
  8. Portaels F, Meyers WM, Ablordey A, Castro AG, Chemlal K, de Rijk P, Elsen P, Fissette K, Fraga AG, Lee R, Mahrous E, Small PL, Stragier P, Torrado E, Van Aerde A, Silva MT, Pedrosa J. First Cultivation and Characterization of Mycobacterium ulcerans from the Environment. PLoS Negl Trop Dis. 2008 Mar 26;2(3):e178.
  9. En J, Goto M, Nakanaga K, Higashi M, Ishii N, Saito H, Yonezawa S, Hamada H, Small PL. Mycolactone is responsible for the painlessness of Mycobacterium ulcerans infection (buruli ulcer) in a murine study. Infect Immun. 2008 May;76(5):2002-7.
  10. Torrado E, Adusumilli S, Fraga AG, Small PL, Castro AG, Pedrosa J. Mycolactone-mediated inhibition of tumor necrosis factor production by macrophages infected with Mycobacterium ulcerans has implications for the control of infection. Infect Immun. 2007 Aug;75(8):3979-88.
  11. Godfrey D, Williamson H, Silverman J, Small PL. Newly identified Mycobacterium species in a Xenopus laevis colony.Comp Med. 2007 Feb;57(1):97-104.
  12. Stinear TP, Seemann T, Pidot S, Frigui W, Reysset G, Garnier T, Meurice G, Simon D, Bouchier C, Ma L, Tichit M, Porter JL, Ryan J, Johnson PD, Davies JK, Jenkin GA, Small PL, Jones LM, Tekaia F, Laval F, Daffé M, Parkhill J, Cole ST. Reductive evolution and niche adaptation inferred from the genome of Mycobacterium ulcerans, the causative agent of Buruli ulcer. Genome Res. 2007 Feb;17(2):192-200. Epub 2007 Jan 8.
  13. Ranger BS, Mahrous EA, Mosi L, Adusumilli S, Lee RE, Colorni A, Rhodes M, Small PL. Globally distributed mycobacterial fish pathogens produce a novel plasmid-encoded toxic macrolide, mycolactone F.Infect Immun. 2006 Nov;74(11):6037-45.
  14. Rybniker J, Kramme S, Small PL. Host range of 14 mycobacteriophages in Mycobacterium ulcerans and seven other mycobacteria including Mycobacterium tuberculosis--application for identification and susceptibility testing. J Med Microbiol. 2006 Jan;55(Pt 1):37-42.
  15. Adusumilli S, Mve-Obiang A, Sparer T, Meyers W, Hayman J, Small PL. Mycobacterium ulcerans toxic macrolide, mycolactone modulates the host immune response and cellular location of M. ulcerans in vitro and in vivo. Cell Microbiol. 2005 Sep;7(9):1295-304.
  16. Coutanceau E, Marsollier L, Brosch R, Perret E, Goossens P, Tanguy M, Cole ST, Small PL, Demangel C. Modulation of the host immune response by a transient intracellular stage of Mycobacterium ulcerans: the contribution of endogenous mycolactone toxin. Cell Microbiol. 2005 Aug;7(8):1187-96.
  17. Marsollier L, Aubry J, Coutanceau E, André JP, Small PL, Milon G, Legras P, Guadagnini S, Carbonnelle B, Cole ST. Colonization of the salivary glands of Naucoris cimicoides by Mycobacterium ulcerans requires host plasmatocytes and a macrolide toxin, mycolactone. Cell Microbiol. 2005 Jul;7(7):935-43.
  18. Mve-Obiang A, Lee RE, Umstot ES, Trott KA, Grammer TC, Parker JM, Ranger BS, Grainger R, Mahrous EA, Small PL. A newly discovered mycobacterial pathogen isolated from laboratory colonies of Xenopus species with lethal infections produces a novel form of mycolactone, the Mycobacterium ulcerans macrolide toxin. Infect Immun. 2005 Jun;73(6):3307-12.
  19. Merritt, R. W., M. E. Benbow, and P. L. C. Small. 2005. Unraveling an emerging disease associated with disturbed aquatic environments: the case of Buruli ulcer. Frontiers in Ecology and the Environment 3: 323-331. Review
  20. Johnson PD, Stinear T, Small PL, Pluschke G, Merritt RW, Portaels F, Huygen K, Hayman JA, Asiedu K. Buruli ulcer (M. ulcerans infection): new insights, new hope for disease control. PLoS Med. 2005 Apr;2(4):e108. Epub 2005 Apr 26. PLoS Med. 2005 May;2(5):e173. Review
  21. Daniel AK, Lee RE, Portaels F, Small PL. Analysis of Mycobacterium species for the presence of a macrolide toxin, mycolactone. Infect Immun. 2004 Jan;72(1):123-32.
  22. van der Werf TS, Stinear T, Stienstra Y, van der Graaf WT, Small PL. Abstract Mycolactones and Mycobacterium ulcerans disease. Lancet. 2003 Sep 27;362(9389):1062-4. Review.
  23. Snyder DS, Small PL. Uptake and cellular actions of mycolactone, a virulence determinant for Mycobacterium ulcerans. Microb Pathog. 2003 Feb;34(2):91-101.
  24. Mve-Obiang A, Lee RE, Portaels F, Small PL. Heterogeneity of mycolactones produced by clinical isolates of Mycobacterium ulcerans: implications for virulence. Infect Immun. 2003 Feb;71(2):774-83.
  25. Cope RB, Hartman JA, Morrow CK, Haschek WM, Small PL. Ultraviolet radiation enhances both the nodular and ulcerative forms of Mycobacterium ulcerans infection in a Crl:IAF(HA)-hrBR hairless guinea pig model of Buruli ulcer disease. Photodermatol Photoimmunol Photomed. 2002 Dec;18(6):271-9.
  26. Cadapan LD, Arslanian RL, Carney JR, Zavala SM, Small PL, Licari P. Suspension cultivation of Mycobacterium ulcerans for the production of mycolactones. FEMS Microbiol Lett. 2001 Dec 18;205(2):385-9.
  27. Dobos KM, Small PL, Deslauriers M, Quinn FD, King CH. Mycobacterium ulcerans cytotoxicity in an adipose cell model. Infect Immun. 2001 Nov;69(11):7182-6.
  28. Fidanze S, Song F, Szlosek-Pinaud M, Small PL, Kishi Y. Complete structure of the mycolactones. J Am Chem Soc. 2001 Oct 17;123(41):10117-8.
  29. Benowitz AB, Fidanze S, Small PL, Kishi Y. Stereochemistry of the core structure of the mycolactones. J Am Chem Soc. 2001 May 30;123(21):5128-9.
  30. George KM, Pascopella L, Welty DM, Small PL. A Mycobacterium ulcerans toxin, mycolactone, causes apoptosis in guinea pig ulcers and tissue culture cells. Infect Immun. 2000 Feb;68(2):877-83.
  31. Pahlevan AA, Wright DJ, Andrews C, George KM, Small PL, Foxwell BM. The inhibitory action of Mycobacterium ulcerans soluble factor on monocyte/T cell cytokine production and NF-kappa B function. J Immunol. 1999 Oct 1;163(7):3928-35.
  32. Barker LP, Porcella SF, Wyatt RG, Small PL. The Mycobacterium marinum G13 promoter is a strong sigma 70-like promoter that is expressed in Escherichia coli and mycobacteria species. FEMS Microbiol Lett. 1999 Jun 1;175(1):79-85.
  33. George KM, Chatterjee D, Gunawardana G, Welty D, Hayman J, Lee R, Small PL. Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence. Science. 1999 Feb 5;283(5403):854-7.
  34. Barker LP, Brooks DM, Small PL. The identification of Mycobacterium marinum genes differentially expressed in macrophage phagosomes using promoter fusions to green fluorescent protein. Mol Microbiol. 1998 Sep;29(5):1167-77.
  35. Judd TC, Bischoff A, Kishi Y, Adusumilli S, Small PL. Structure determination of mycolactone C via total synthesis. Org Lett. 2004 Dec 23;6(26):4901-4.
  36. Stinear TP, Mve-Obiang A, Small PL, Frigui W, Pryor MJ, Brosch R, Jenkin GA, Johnson PD, Davies JK, Lee RE, Adusumilli S, Garnier T, Haydock SF, Leadlay PF, Cole ST. Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans. Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1345-9.
  37. Tønjum T, Welty DB, Jantzen E, Small PL. Differentiation of Mycobacterium ulcerans, M. marinum, and M. haemophilum: mapping of their relationships to M. tuberculosis by fatty acid profile analysis, DNA-DNA hybridization, and 16S rRNA gene sequence analysis. J Clin Microbiol. 1998 Apr;36(4):918-25.
  38. George KM, Barker LP, Welty DM, Small PL. Partial purification and characterization of biological effects of a lipid toxin produced by Mycobacterium ulcerans. Infect Immun. 1998 Feb;66(2):587-93.