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Open Access Research article

Virulence-related Mycobacterium avium subsp hominissuis MAV_2928 gene is associated with vacuole remodeling in macrophages

Samradhni S Jha1, Lia Danelishvili1, Dirk Wagner2, Jörg Maser3, Yong-jun Li4, Ivana Moric3, Steven Vogt3, Yoshitaka Yamazaki5, Barry Lai3 and Luiz E Bermudez16*

Author affiliations

1 Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis OR 97331, USA

2 Department of Internal Medicine II—Infectious Diseases, University of Freiburg, 79106 Freiburg, Germany

3 Argonne National Laboratory, Argonne, Illinois, USA

4 Geron Corporation, 230 Constitution Drive, Menlo Park, CA 94025, USA

5 Department of Respiratory and Infectious Diseases, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

6 Department of Microbiology, College of Science, Oregon State University, Corvallis OR 97331, USA

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Citation and License

BMC Microbiology 2010, 10:100  doi:10.1186/1471-2180-10-100

Published: 1 April 2010

Abstract

Background

Mycobacterium avium subsp hominissuis (previously Mycobacterium avium subsp avium) is an environmental organism associated with opportunistic infections in humans. Mycobacterium hominissuis infects and replicates within mononuclear phagocytes. Previous study characterized an attenuated mutant in which the PPE gene (MAV_2928) homologous to Rv1787 was inactivated. This mutant, in contrast to the wild-type bacterium, was shown both to have impaired the ability to replicate within macrophages and to have prevented phagosome/lysosome fusion.

Results

MAV_2928 gene is primarily upregulated upon phagocytosis. The transcriptional profile of macrophages infected with the wild-type bacterium and the mutant were examined using DNA microarray, which showed that the two bacteria interact uniquely with mononuclear phagocytes. Based on the results, it was hypothesized that the phagosome environment and vacuole membrane of the wild-type bacterium might differ from the mutant. Wild-type bacterium phagosomes expressed a number of proteins different from those infected with the mutant. Proteins on the phagosomes were confirmed by fluorescence microscopy and Western blot. The environment in the phagosome of macrophages infected with the mutant differed from the environment of vacuoles with M. hominissuis wild-type in the concentration of zinc, manganese, calcium and potassium.

Conclusion

The results suggest that the MAV_2928 gene/operon might participate in the establishment of bacterial intracellular environment in macrophages.