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


CONCLUSIONS
The results suggest that the MAV_2928 gene/operon might participate in the establishment of bacterial intracellular environment in macrophages.
Jha
Samradhni S
SS
Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
Danelishvili
Lia
L
Wagner
Dirk
D
Maser
Jörg
J
Li
Yong-jun
YJ
Moric
Ivana
I
Vogt
Steven
S
Yamazaki
Yoshitaka
Y
Lai
Barry
B
Bermudez
Luiz E
LE
D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D009000:Monocytes / Q000382:microbiology*; D009162:Mycobacterium avium / Q000472:pathogenicity*; D014617:Vacuoles / Q000378:metabolism* / Q000382:microbiology*; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
D001426:Bacterial Proteins; D037521:Virulence Factors