Research Article: The role of microsporidian polar tube protein 4 (PTP4) in host cell infection

Date Published: April 20, 2017

Publisher: Public Library of Science

Author(s): Bing Han, Valérie Polonais, Tatsuki Sugi, Rama Yakubu, Peter M. Takvorian, Ann Cali, Keith Maier, Mengxian Long, Matthew Levy, Herbert B. Tanowitz, Guoqing Pan, Frédéric Delbac, Zeyang Zhou, Louis M. Weiss, Emily R. Troemel.

http://doi.org/10.1371/journal.ppat.1006341

Abstract

Microsporidia have been identified as pathogens that have important effects on our health, food security and economy. A key to the success of these obligate intracellular pathogens is their unique invasion organelle, the polar tube, which delivers the nucleus containing sporoplasm into host cells during invasion. Due to the size of the polar tube, the rapidity of polar tube discharge and sporoplasm passage, and the absence of genetic techniques for the manipulation of microsporidia, study of this organelle has been difficult and there is relatively little known regarding polar tube formation and the function of the proteins making up this structure. Herein, we have characterized polar tube protein 4 (PTP4) from the microsporidium Encephalitozoon hellem and found that a monoclonal antibody to PTP4 labels the tip of the polar tube suggesting that PTP4 might be involved in a direct interaction with host cell proteins during invasion. Further analyses employing indirect immunofluorescence (IFA), enzyme-linked immunosorbent (ELISA) and fluorescence-activated cell sorting (FACS) assays confirmed that PTP4 binds to mammalian cells. The addition of either recombinant PTP4 protein or anti-PTP4 antibody reduced microsporidian infection of its host cells in vitro. Proteomic analysis of PTP4 bound to host cell membranes purified by immunoprecipitation identified transferrin receptor 1 (TfR1) as a potential host cell interacting partner for PTP4. Additional experiments revealed that knocking out TfR1, adding TfR1 recombinant protein into cell culture, or adding anti-TfR1 antibody into cell culture significantly reduced microsporidian infection rates. These results indicate that PTP4 is an important protein competent of the polar tube involved in the mechanism of host cell infection utilized by these pathogens.

Partial Text

Since the first microsporidium, Nosema bombycis, was discovered in the European silkworm industry in the 19th century [1], more than 1400 species of microsporidia have been identified worldwide [2, 3]. They are ubiquitous obligate intracellular parasites responsible for a variety of diseases both in immune compromised and immune competent individuals. Microsporidia are also responsible for economic losses due to their adverse effects on farming and other industries [4, 5]. Phylogenetic studies suggest that microsporidia are related to fungi, being either a basal branch or sister group [6–13].

Microsporidia possess a unique invasion apparatus, the polar tube. Under the appropriate environmental stimulation, the polar tube can discharge rapidly out of microsporidia spore, form a hollow tube and serve as a conduit for the passage of sporoplasm and nuclear material into a new host cell [51]. Before germination, within the spore, the polar tube is filled with material that has been hypothesized to consist of unpolymerized polar tube proteins and during the process of germination and extrusion of the polar tube this filled structure transitions to a hollow tube [23, 55]. The length of discharged polar tubes is approximately 2 to 3 times that of the coiled tubes inside the spore and it has been hypothesized that either unpolymerized polar tube proteins are incorporated at the growing tip of polar tube during discharge or that the tube unfolds during eversion [23, 27, 28, 55]. In the process of polar tube eversion, unique immunologic epitopes may be exposed on polar tube proteins [10].

 

Source:

http://doi.org/10.1371/journal.ppat.1006341

 

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