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The Chlamydia trachomatis IncM Protein Interferes with Host Cell Cytokinesis, Centrosome Positioning, and Golgi Distribution and Contributes to the Stability of the Pathogen-Containing Vacuole
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Resumo(s)
Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes ocular and urogenital infections in humans. The ability of C. trachomatis to grow intracellularly in a pathogen-containing vacuole (known as an inclusion) depends on chlamydial effector proteins transported into the host cell by a type III secretion system. Among these effectors, several inclusion membrane proteins (Incs) insert in the vacuolar membrane. Here, we show that human cell lines infected by a C. trachomatis strain deficient for Inc CT288/CTL0540 (renamed IncM) displayed less multinucleation than when infected by IncM-producing strains (wild type or complemented). This indicated that IncM is involved in the ability of Chlamydia to inhibit host cell cytokinesis. The capacity of IncM to induce multinucleation in infected cells was shown to be conserved among its chlamydial homologues and appeared to require its two larger regions predicted to be exposed to the host cell cytosol. C. trachomatis-infected cells also displayed IncM-dependent defects in centrosome positioning, Golgi distribution around the inclusion, and morphology and stability of the inclusion. The altered morphology of inclusions containing IncM-deficient C. trachomatis was further affected by depolymerization of host cell microtubules. This was not observed after depolymerization of microfilaments, and inclusions containing wild-type C. trachomatis did not alter their morphology upon depolymerization of microtubules. Overall, these findings suggest that IncM may exert its effector function by acting directly or indirectly on host cell microtubules.
Descrição
We thank Irina Franco for critical reading of the manuscript and Agathe Subtil, Guangming Zhong, Ian Clarke, and Joao Paulo Gomes for gifts of antibodies and chlamydial genomic DNA. This work was supported by Fundacao para a Ciencia e a Tecnologia (FCT) in the scope of project UIDB/ 04378/2020 of the Research Unit on Applied Molecular Biosciences, UCIBIO, and LA/P/0140/ 2020 of the Associate Laboratory Institute for Health and Bioeconomy, i4HB. M.P.L. and I.S.P. were supported by PhD fellowships. J.N.B. was supported within the scope of the PhD program Molecular Biosciences (PD/00133/2012), also funded by FCT.
Palavras-chave
Immunology Infectious Diseases centrosomes Chlamydia bacterial pathogenesis