Mycobacterium tuberculosis produces pili during human infection

doi:10.1073/pnas.0602304104

Mycobacterium tuberculosis produces pili during human infection

*Department of Immunobiology, University of Arizona, 1501 North Campbell Avenue, LSN 649, Tucson, AZ 85724;
^‡Proteomics and Mass Spectrometry Facility, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; and
^§Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, 64010, Mexico

Edited by Barry R. Bloom, Harvard School of Public Health, Boston, MA, and approved January 17, 2007 (received for review March 21, 2006)

Abstract

Mycobacterium tuberculosis is responsible for nearly 3 million human deaths worldwide every year. Understanding the mechanisms and bacterial factors responsible for the ability of M. tuberculosis to cause disease in humans is critical for the development of improved treatment strategies. Many bacterial pathogens use pili as adherence factors to colonize the host. We discovered that M. tuberculosis produces fine (2- to 3-nm-wide), aggregative, flexible pili that are recognized by IgG antibodies contained in sera obtained from patients with active tuberculosis, indicating that the bacilli produce pili or pili-associated antigen during human infection. Purified M. tuberculosis pili (MTP) are composed of low-molecular-weight protein subunits encoded by the predicted M. tuberculosis H37Rv ORF, designated Rv3312A. MTP bind to the extracellular matrix protein laminin in vitro, suggesting that MTP possess adhesive properties. Isogenic mtp mutants lost the ability to produce Mtp in vitro and demonstrated decreased laminin-binding capabilities. MTP shares morphological, biochemical, and functional properties attributed to bacterial pili, especially with curli amyloid fibers. Thus, we propose that MTP are previously unidentified host-colonization factors of M. tuberculosis.

Footnotes

^†To whom correspondence should be sent at the present address:
University of Michigan Medical School, Department of Microbiology and Immunology, 5641 Medical Science II, 1150 West Medical Center Drive, Ann Arbor, MI 48109.
E-mail: alteri{at}umich.edu
Author contributions: J.A.G. and R.L.F. contributed equally to this work; C.J.A., J.A.G., and R.L.F. designed research; C.J.A., J.X.-C., and S.H. performed research; S.H. and G.C.-O. contributed new reagents/analytic tools; C.J.A., S.H., J.A.G., and R.L.F. analyzed data; and C.J.A., J.A.G., and R.L.F. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS direct submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0602304104/DC1.
Abbreviations:

ECM,

extracellular matrix;

IF,

immunofluorescence;

MTP,

M. tuberculosis pili;

TEM,

transmission electron microscopy.
Freely available online through the PNAS open access option.