HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Singh, P. P. Articles by Brennan, M. J. Search for Related Content PubMed PubMed Citation Articles by Singh, P. P. Articles by Brennan, M. J. Agricola Articles by Singh, P. P. Articles by Brennan, M. J.

A comparative study of host response to three Mycobacterium tuberculosis PE_PGRS proteins

Michael J. Brennan

Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20910, USA

Correspondence
Michael J. Brennan
mbrennan{at}aeras.org

Three Mycobacterium tuberculosis proteins, PE_PGRS 16 (Rv0977), PE_PGRS 26 (Rv1441c) and PE_PGRS 33 (Rv1818c), were expressed in Mycobacterium smegmatis and used to investigate the host response to members of this unique protein family. Following infection of macrophages with the recombinant M. smegmatis (Ms) strains, Ms-PE_PGRS 33 and Ms-PE_PGRS 26 were significantly more persistent (4.4 and 4.2 log c.f.u.) compared with Ms-PE_PGRS 16 (3.4 log c.f.u.) at day 6. Similarly, after infection of mice, Ms-PE_PGRS 33 and Ms-PE_PGRS 26 persisted at significantly higher levels in the spleen (3.5 and 3.2 log c.f.u.) and liver (3 and 2.6 log c.f.u.) compared with Ms-PE_PGRS 16 in the spleen (2 log c.f.u.) and in the liver (1 log c.f.u.) at day 10. Increased persistence of Ms-PE_PGRS 33 and Ms-PE_PGRS 26 was associated with cell death and increased release of lactate dehydrogenase in macrophage cultures as well as increased levels of IL-10 and, in contrast, lower levels of IL-12 and NO both in vitro and in mouse splenocytes. Conversely, poor survival of Ms-PE_PGRS 16 was associated both in macrophage cultures and in vivo with higher levels of NO and IL-12. All three PE_PGRS proteins were found to be cell-surface antigens, but immunization of mice with these PE_PGRS antigens as DNA vaccines showed no protection in a TB aerosol challenge model. In general, the results suggest that variable expression of different PE_PGRS proteins within host cells can affect either the fate of the mycobacterial pathogen or that of the host during infection and point to the importance of studying the expression and function of individual members of the PE_PGRS gene family of M. tuberculosis.

Present address: Aeras Global TB Vaccine Foundation, 1405 Research Boulevard, Suite 300, Rockville, MD 20850, USA.

A table of primers and a supplementary figure are available with the online version of this paper.

This article has been cited by other articles:

				O. Chacon, L. E. Bermudez, D. K. Zinniel, H. K. Chahal, R. J. Fenton, Z. Feng, K. Hanford, L. G. Adams, and R. G. Barletta Impairment of D-alanine biosynthesis in Mycobacterium smegmatis determines decreased intracellular survival in human macrophages Microbiology, May 1, 2009; 155(5): 1440 - 1450. [Abstract] [Full Text] [PDF]