Education

PhD (Organic Chemistry)
Northwestern University, Evanston, Ill. 1966
Postgraduate Training
ARGC Postdoctoral Fellow, Department of Biochemistry, University of Queensland, Brisbane, Australia, 1966-1970

Areas of Interests

Research Interests

Tuberculosis

Research Information

Tuberculosis

M. tuberculosis (MTB) is surrounded by a thick and hard lipid coat. Consequently, the bacteria are well shielded from the immune system and antibiotics resulting in difficult and prolonged therapy regimens. Electron and light microscopy studies provide conclusive evidence that certain surfactants effectively and rapidly remove their protective armor thus offering a novel fast acting, targeted treatment modality for pulmonary TB.

tb20

Appearance of TB bacteria grown in media in the absence of detergent. Instead of a net-like appearance, they are more condensed in amorphous structures of enormous size. Sonication ruptures their protective coat to reveal the content of MTB that resides inside.

MTB owes its tenacity to a relatively thick, waxy, hard lipid coat named trehalose dimycolate (TDM) which very effectively protects the bacteria from the immune system and antibiotics. This armor is also its Achilles’ heel. Accordingly, we propose a direct, rapid and localized approach to treat pulmonary TB in which the bacteria are stripped of their shield by direct exposure to surfactants introduced into the lung. In this regard, surfactants have been established since the early 60’s as an efficient method of disrupting lipid bilayers and have a long history of use as the principle means to extract and isolate proteins from cellular membranes. Thus, in this study we have evaluated the proficiency of certain surfactants to disrupt MTB’s membrane and to gauge their toxicity in the lungs of mice. The surfactants exhibit no toxicity under conditions that
are bactericidal to MTB. Our electron and light microscopy studies of MTB further support our contention that certain surfactants offer a novel, fast acting, targeted treatment modality that is well suited for breaching the bacteria’s armor and exposing them to antibiotics and the immune response for an uncharacteristic rapid clearance of the disease.

Publications

Publication Information

References

  • Semyou A. Risin, Robert L. Hunter, Mikhail Kobak, Boris Ariel, Boris Vishnevsky, Alvdislav Erokhin, Olga Demikhova, Irina Bacharova, and James K. Stoops2014, Certain Surfactants Significantly Enhance the Activity of Antibiotics in the Mouse Model of MTB and Drug Resistant MTB Infection and Effectively Remove the Bacteria from a Pulmonary Cavity in Human Ex-Vivo Study. Annals of Clinical and Laboratory Science, Vol 44, 117-122.
  • Stoops, James K., Arora, Ranjana, Armitige, Lisa, Wanger, Audrey, Song, Ling, Blackburn, Michael R., Krueger, Gerhard R., and Risin, Semyon A. 2010, Certain Surfactants Show Promise in the Therapy of Pulmonary Tuberculosis. In Vivo; 24:687-694.
  • Yu, Xuekui, Hiromosa, Y. , Tsen, Hus, Stoops, James K.,  Roche, Thomas E., and Zhou, Hong Z.,  2008, Structures of the Pyruvate Dehydrogenase Complex Cores: A Highly Conserved Catalytic Center with N-Terminal Domains. Structure 16: 1-11.
  • Pullan, L., Mullapudi, S., Huang, Z., Baldwin, P.R., Chin, C., Sun, W., Tsujimoto, S., Kolodziej, S.J., Stoops, J.K., Lee, J.C., Waxham, M.N., Bean, A.J., and Penczek, P.A. 2006, The Endosome-Associated Protein Hrs Is Hexameric and Controls Cargo Sorting as a “Master Molecule”. Structure 14: 661-671.
  • Zhou, Z.H., Stoops, J.K. and Krueger, G.R.F., 2006, Ultrastructure and Assembly of Human Herpesvirus-6 (HHV-6). In Perspective Medical Virology 12, pp 11-21, Eds. G. Krueger and D. Ablashi, Elsevier, Amsterdam.