High-level heterologous expression and secretion in rapidly growing nonpathogenic mycobacteria of four major Mycobacterium tuberculosis extracellular proteins considered to be leading vaccine candidates and drug targets.

Infection and Immunity
G HarthM A Horwitz

Abstract

Mycobacterium tuberculosis, the primary etiologic agent of tuberculosis, is the world's leading cause of death from a single infectious agent, and new vaccines and drugs to combat it are urgently needed. The major extracellular proteins of M. tuberculosis, which are released into its phagosome in macrophages, its host cells in humans, are leading candidates for a vaccine and prime targets for new drugs. However, the development of these biologicals has been hampered by the unavailability of large quantities of recombinant extracellular proteins identical to their native counterparts. In this report, we describe the heterologous expression and secretion of four major M. tuberculosis extracellular proteins (the 30-, 32, 16-, and 23.5-kDa proteins--the first, second, third, and eighth most abundant, respectively) in rapidly growing, nonpathogenic mycobacterial species. Multiple attempts to obtain secretion of the proteins by using Escherichia coli- and Bacillus subtilis-based expression systems were unsuccessful, suggesting that high-level expression and secretion of these Mycobacterium-specific proteins require a mycobacterial host. All four recombinant proteins were stably expressed from the cloned genes' own promoters at yields...Continue Reading

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Citations

Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicole D PecoraClifford V Harding
Feb 2, 2011·Assay and Drug Development Technologies·Deborah MaiAdrie J C Steyn
Oct 31, 2012·Journal of Separation Science·Chih-Wei ChiuSung-Fang Chen
Apr 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Günter HarthMarcus A Horwitz
Jul 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Amit SinghAdrie J C Steyn
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Jan 26, 2000·Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie·J Hess, S H Kaufmann
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Aug 11, 2019·Microbiology Spectrum·Vincent J C van WindenMiriam Braunstein
Aug 9, 2003·Journal of Clinical Microbiology·Claus AagaardJohn M Pollock
Mar 22, 2003·Journal of the American Society for Mass Spectrometry·Ying GeClifton E Barry

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