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Journal of Bacteriology, March 2006, p. 1856-1865, Vol. 188, No. 5
0021-9193/06/$08.00+0     doi:10.1128/JB.188.5.1856-1865.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Mycobacterium tuberculosis Cells Growing in Macrophages Are Filamentous and Deficient in FtsZ Rings

Ashwini Chauhan,1 Murty V. V. S. Madiraju,1 Marek Fol,1 Hava Lofton,1 Erin Maloney,1 Robert Reynolds,2 and Malini Rajagopalan1*

Biomedical Research, The University of Texas Health Center at Tyler, Tyler, Texas 75708-3154,1 Drug Discovery Division, Southern Research Institute, Birmingham, Alabama 352052

Received 8 November 2005/ Accepted 12 December 2005

FtsZ, a bacterial homolog of tubulin, forms a structural element called the FtsZ ring (Z ring) at the predivisional midcell site and sets up a scaffold for the assembly of other cell division proteins. The genetic aspects of FtsZ-catalyzed cell division and its assembly dynamics in Mycobacterium tuberculosis are unknown. Here, with an M. tuberculosis strain containing FtsZTB tagged with green fluorescent protein as the sole source of FtsZ, we examined FtsZ structures under various growth conditions. We found that midcell Z rings are present in approximately 11% of actively growing cells, suggesting that the low frequency of Z rings is reflective of their slow growth rate. Next, we showed that SRI-3072, a reported FtsZTB inhibitor, disrupted Z-ring assembly and inhibited cell division and growth of M. tuberculosis. We also showed that M. tuberculosis cells grown in macrophages are filamentous and that only a small fraction had midcell Z rings. The majority of filamentous cells contained nonring, spiral-like FtsZ structures along their entire length. The levels of FtsZ in bacteria grown in macrophages or in broth were comparable, suggesting that Z-ring formation at midcell sites was compromised during intracellular growth. Our results suggest that the intraphagosomal milieu alters the expression of M. tuberculosis genes affecting Z-ring formation and thereby cell division.

* Corresponding author. Mailing address: Biomedical Research, The University of Texas Health Center at Tyler, Tyler, TX 75708-3154. Phone: (903) 877-7731. Fax: (903) 877-5969. E-mail: malini.rajagopalan{at}uthct.edu.

Journal of Bacteriology, March 2006, p. 1856-1865, Vol. 188, No. 5
0021-9193/06/$08.00+0     doi:10.1128/JB.188.5.1856-1865.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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