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

Journal Article · · BMC Microbiology
 [1];  [2];  [3];  [4];  [5];  [4];  [4];  [6];  [4];  [7]
  1. Oregon State Univ., Corvallis, OR (United States). College of Veterinary Medicine. Dept. of Biomedical Sciences; DOE/OSTI
  2. Oregon State Univ., Corvallis, OR (United States). College of Veterinary Medicine. Dept. of Biomedical Sciences
  3. Univ. of Freiburg (Germany). Dept. of Internal Medicine II. Infectious Diseases
  4. Argonne National Lab. (ANL), Argonne, IL (United States)
  5. Geron Corporation, Menlo Park, CA (United States)
  6. Shinshu Univ. Matsumoto (Japan). School of Medicine. Dept. of Respiratory and Infectious Diseases
  7. Oregon State Univ., Corvallis, OR (United States). College of Veterinary Medicine. Dept. of Biomedical Sciences; Oregon State Univ., Corvallis, OR (United States). College of Science. Dept. of Microbiology
+ Show Author Affiliations

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1626476
Journal Information:
BMC Microbiology, Journal Name: BMC Microbiology Journal Issue: 1 Vol. 10; ISSN 1471-2180
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

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The Voltage-Dependent Anion Channels (VDAC) of Mycobacterium avium phagosome are associated with bacterial survival and lipid export in macrophages journal August 2017
Illegitimate recombination: An efficient method for random mutagenesis in Mycobacterium avium subsp. hominissuis journal September 2012
A comparative study of Mycobacterium avium subsp. avium and Mycobacterium avium subsp. hominissuis in experimentally infected pigs journal January 2012
Evolution of Smooth Tubercle Bacilli PE and PE_PGRS Genes: Evidence for a Prominent Role of Recombination and Imprint of Positive Selection journal May 2013
Responses of Bovine Innate Immunity to Mycobacterium avium subsp. paratuberculosis Infection Revealed by Changes in Gene Expression and Levels of MicroRNA journal October 2016
Structural Characteristics, Binding Partners and Related Diseases of the Calponin Homology (CH) Domain journal May 2020
PE11 (Rv1169c) selectively alters fatty acid components of Mycobacterium smegmatis and host cell interleukin-6 level accompanied with cell death journal June 2015
Mycobacterium tuberculosis Co-operonic PE32/PPE65 Proteins Alter Host Immune Responses by Hampering Th1 Response journal May 2016
Immunoregulatory functions and expression patterns of PE/PPE family members: Roles in pathogenicity and impact on anti-tuberculosis vaccine and drug design: Expression And Functions Of Mycobacterial Pe/Ppe Proteins journal June 2015
Leucine-rich repeats and calponin homology containing 4 (Lrch4) regulates the innate immune response journal February 2019
Comparative genomic and proteomic analyses of PE/PPE multigene family of Mycobacterium tuberculosis H37Rv and H37Ra reveal novel and interesting differences with implications in virulence journal May 2012
Mycobacteria and the Intraphagosomal Environment: Take It With a Pinch of Salt(s)!: Sensing and Regulation of the Intraphagosomal Environment journal April 2012
Phylogeny to function: PE/PPE protein evolution and impact on M ycobacterium tuberculosis pathogenicity: Evolution of PE/PPE-associated virulence journal March 2015
Mycobacteria and the Intraphagosomal Environment: Take It With a Pinch of Salt(s)! journal May 2013
Mycobacterial PE/PPE Proteins at the Host-Pathogen Interface journal January 2011
BINDER: computationally inferring a gene regulatory network for Mycobacterium abscessus journal September 2019

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