Characterization of Mce4A protein of <it>Mycobacterium tuberculosis</it>: role in invasion and survival

<p>Abstract</p> <p>Background</p> <p>The <it>mce4 </it>operon is one of the four homologues of mammalian cell entry (<it>mce</it>) operons of <it>Mycobacterium tuberculosis</it>. The <it>mce4A </it>(Rv3499c) gene within th...

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Main Authors: Pasricha Rashmi, Chandolia Amita, Sharma Monika, Saini Neeraj, Brahmachari Vani, Bose Mridula
Format: Article
Language:English
Published: BMC 2008-11-01
Series:BMC Microbiology
Online Access:http://www.biomedcentral.com/1471-2180/8/200
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Summary:<p>Abstract</p> <p>Background</p> <p>The <it>mce4 </it>operon is one of the four homologues of mammalian cell entry (<it>mce</it>) operons of <it>Mycobacterium tuberculosis</it>. The <it>mce4A </it>(Rv3499c) gene within this operon is homologous to <it>mce1A </it>(Rv0169), that has a role in host cell invasion by <it>M. tuberculosis</it>. Our earlier reports show that <it>mce4 </it>operon is expressed during the stationary phase of growth of the bacillus in culture and during the course of infection in mammalian hosts. <it>M. tuberculosis </it>carrying mutation in <it>mce4 </it>operon shows growth defect and reduced survival in infected mice. However, the intracellular localization of Mce4A protein and its direct role in cell entry or survival of the bacillus has not been demonstrated so far.</p> <p>Results</p> <p>By transmission electron microscopy we have demonstrated that recombinant Mce4A protein facilitates the invasion of non-pathogenic strain of <it>E. coli </it>into non-phagocytic HeLa cells. We observe that <it>mce4A </it>gene has a role comparable to <it>mce1A </it>in the survival of recombinant <it>E. coli </it>in human macrophages. Using antibodies raised against Mce4A protein, we show that the protein is localized in the cell wall fraction of <it>M. tuberculosis </it>H37Rv stationary phase culture only.</p> <p>Conclusion</p> <p>Mce4A protein is expressed during the stationary phase of broth culture and localizes in the cell wall fraction of <it>M. tuberculosis</it>. Mce4A protein expressed in non-pathogenic <it>E. coli </it>enables it to enter and survive within HeLa cells and the macrophages. As Mce4A protein is expressed during later phase of mycobacterial growth, our results raise the possibility of it playing a role in maintenance of persistent tubercular infection.</p>
ISSN:1471-2180