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Infection and Immunity, December 2002, p. 6751-6760, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6751-6760.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Decreased Infectivity despite Unaltered C3 Binding by a hbhA Mutant of Mycobacterium tuberculosis

Stacey L. Mueller-Ortiz,^1,2, Eliud Sepulveda,² Margaret R. Olsen,² Chinnaswamy Jagannath,² Audrey R. Wanger,^1,2 and Steven J. Norris^1,2*

Graduate School of Biomedical Sciences,¹ Department of Pathology and Laboratory Medicine, Medical School, University of Texas Health Science Center at Houston, Houston, Texas 77030²

Received 3 May 2002/ Returned for modification 20 August 2002/ Accepted 12 September 2002

HbhA of Mycobacterium tuberculosis is a multifunctional binding protein, binding to both sulfated sugars such as heparin and to human complement component C3. HbhA may therefore interact with host molecules and/or host cells during M. tuberculosis infection and play a role in the pathogenesis of this bacterium. The purpose of this study was to use allelic exchange to create an M. tuberculosis strain deficient in expression of HbhA to determine whether this protein's C3-binding activity plays a role in the pathogenesis of M. tuberculosis. An in-frame, 576-bp unmarked deletion in the hbhA gene was created using sacB as a counterselectable marker. Southern blotting and PCR analyses confirmed deletion of hbhA in the hbhA mutant. The hbhA mutant strain grew at a rate similar to that of the parent in broth culture and in J774.A1 murine macrophage-like cells but was deficient in growth compared to the parent strain in the lungs, liver, and spleen of infected mice. In addition, the hbhA mutation did not reduce binding of M. tuberculosis to human C3 or to J774.A1 cells in the presence or absence of serum, suggesting that in the absence of HbhA, other molecules serve as C3-binding molecules on the M. tuberculosis surface. Taken together, these data indicate that HbhA is important in the infectivity of M. tuberculosis, but its ability to bind C3 is not required for mycobacterial adherence to macrophage-like cells. Using the hbhA mutant strain, a second M. tuberculosis C3-binding protein similar in size to HbhA was identified as HupB, but the role of HupB as a C3-binding protein in intact organisms remains to be determined.

Editor: S. H. E. Kaufmann

Present address: Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030.

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