Intracellular passage within macrophages affects the trafficking of virulent tubercle bacilli upon reinfection of other macrophages in a serum-dependent manner

Abstract 

Setting: The interaction of tubercle bacilli with macrophages is central to understanding of tuberculosis disease.

Objective: The objective was to determine whether prior passage within macrophages affects the behavior of Mycobacterium tuberculosis (Mtb) upon re-entry into other macrophages.

Design: Transmission electron microscopy was used to monitor fusion of bacterial phagosomes with late endosomal/lysosomal compartments using thoria as a fluid phase marker. Two-dimensional polyacrylamide gel electrophoresis was used to study bacterial protein expression within macrophages.

Results: H37Rv and BCG expressed novel proteins within macrophages. H37Rv also underwent less fusion after intracellular (IC) (24.2±7.7%) than extracellular (XC) (67.4±5.5%) passage when the bacteria entered new macrophages in small clusters. These effects were inhibited by serum, and were not observed with H37Ra or BCG bacteria (78.9±1.6% fused for all conditions). In addition, vacuoles which contained single bacilli were less likely to acquire markers (26.9±2.6%) than those that contained multiple bacilli (77.3±2.8%).

Conclusion: These results indicate that phagolysosomal fusion patterns can be modulated by a variety of factors and that virulent Mtb bacteria may express proteins within macrophages that alter their interaction with these host cells.

No full text is available. To read the body of this article, please view the PDF online.

• f1 Correspondence to: K.A. McDonough, Wadsworth Center, PO Box 22002, 120 New Scotland Avenue, Albany, NY 12201-2002, USA. Tel.: +518 486 4253; Fax: +518 474 3181; E-mail: kathleen.mcdonough@wadsworth.org