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Open Access Highly Accessed Research article

Gene expression profiling of Mycobacterium avium subsp. paratuberculosis in simulated multi-stress conditions and within THP-1 cells reveals a new kind of interactive intramacrophage behaviour

Andrea Cossu1*, Leonardo Antonio Sechi1, Stefania Zanetti1 and Valentina Rosu12

Author Affiliations

1 Department of Biomedical Sciences, Division of Experimental and Clinical Microbiology, University of Sassari, Sassari, Italy

2 Experimental Zooprophylactic Institute of Sardinia, Department of Nuoro, Nuoro, Italy

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BMC Microbiology 2012, 12:87  doi:10.1186/1471-2180-12-87

Published: 30 May 2012

Abstract

Background

Recent studies have identified in Mycobacterium avium subsp. paratuberculosis (MAP), already known as a pathogen in ruminants, a potential zoonotic agent of some autoimmune diseases in humans. Therefore, considering the possible risk for public health, it is necessary a thorough understanding of MAP's gene expression during infection of human host as well as the identification of its immunogenic and/or virulence factors for the development of appropriate diagnostic and therapeutic tools.

Results

In order to characterize MAP's transcriptome during macrophage infection, we analyzed for the first time the whole gene expression of a human derived strain of MAP in simulated intraphagosomal conditions and after intracellular infection of the human macrophage cell line THP-1 by using the DNA-microarray technology. Results showed that MAP shifts its transcriptome to an adaptive metabolism for an anoxic environment and nutrient starvation. It up-regulates several response factors to oxidative stress or intracellular conditions and allows, in terms of transcription, a passive surface peptidoglycan spoliation within the macrophage along with an intensification of the anabolic activity for lipidic membrane structures.

Conclusions

These results indicate a possible interactive system between MAP and its host cell based on the internal mimicry unlike other intracellular pathogens, bringing new hypothesis in the virulence and pathogenicity of MAP and its importance in human health.

Keywords:
Mycobacterium avium subsp. paratuberculosis; functional genomics; DNA-microarray; simulated intra-phagosomal multi-stress; macrophage infection