Abstract
BackgroundThe mce4 operon is one of the four homologues of mammalian cell entry (mce) operons of Mycobacterium tuberculosis. The mce4A (Rv3499c) gene within this operon is homologous to mce1A (Rv0169), that has a role in host cell invasion by M. tuberculosis. Our earlier reports show that mce4 operon is expressed during the stationary phase of growth of the bacillus in culture and during the course of infection in mammalian hosts. M. tuberculosis carrying mutation in mce4 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.ResultsBy transmission electron microscopy we have demonstrated that recombinant Mce4A protein facilitates the invasion of non-pathogenic strain of E. coli into non-phagocytic HeLa cells. We observe that mce4A gene has a role comparable to mce1A in the survival of recombinant E. coli in human macrophages. Using antibodies raised against Mce4A protein, we show that the protein is localized in the cell wall fraction of M. tuberculosis H37Rv stationary phase culture only.ConclusionMce4A protein is expressed during the stationary phase of broth culture and localizes in the cell wall fraction of M. tuberculosis. Mce4A protein expressed in non-pathogenic E. coli 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.
Highlights
The mce4 operon is one of the four homologues of mammalian cell entry operons of Mycobacterium tuberculosis
Earlier we reported the expression of mce4 and absence of mce1 transcripts in the specific tissues of both infected rabbits and guinea pigs during advanced disease conditions, which suggested that mce4 operon, may have a role in the long term survival of M. tuberculosis in host's tissue [11]
It is demonstrated that deletion mutants of mce3 and mce4 operons of M. tuberculosis H37Rv are attenuated in mice [13]
Summary
The mce operon is one of the four homologues of mammalian cell entry (mce) operons of Mycobacterium tuberculosis. Our earlier reports show that mce operon is expressed during the stationary phase of growth of the bacillus in culture and during the course of infection in mammalian hosts. The World Health Organization has estimated that nearly one-third of the world's population is latently infected with Mycobacterium tuberculosis and 8–10 million people develop active disease resulting in 2 million deaths each year [1,2]. Role of Mce1A protein in the entry and survival of the pathogen is demonstrated using recombinant E. coli carrying cloned copy of the gene as well as latex microspheres coated with recombinant Mce1A protein, both of which were able to enter HeLa cells [8,9]. Direct involvement of individual proteins from mce operon in the survival or uptake of M. tuberculosis into the mammalian cells was not demonstrated
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