Chlamydiapreserves the mitochondrial network necessary for replication via microRNA-dependent inhibition of fission.
Obligate intracellular bacteria such asChlamydia trachomatisdepend on metabolites of the host cell and thus protect their sole replication niche by interfering with the host cells' stress response. Here, we investigated the involvement of host microRNAs (miRNAs) in maintaining the viability ofC. trachomatis-infected primary human cells. We identified miR-30c-5p as a prominently up-regulated miRNA required for the stable down-regulation of p53, a major suppressor of metabolite supply inC. trachomatis-infected cells. Loss of miR-30c-5p led to the up-regulation of Drp1, a mitochondrial fission regulator and a target gene of p53, which, in turn, severely affected chlamydial growth and had a marked effect on the mitochondrial network. Drp1-induced mitochondrial fragmentation prevented replication ofC. trachomatiseven in p53-deficient cells. Additionally,Chlamydiamaintain mitochondrial integrity during reactive oxygen species-induced stress that occurs naturally during infection. We show thatC. trachomatisrequire mitochondrial ATP for normal development and hence postulate that they preserve mitochondrial integrity through a miR-30c-5p-dependent inhibition of Drp1-mediated mitochondrial fission.
Department of Microbiology, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
Suvagata Roy
SR
Chowdhury
Department of Microbiology, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
Anastasija
A
Reimer
Institute for Molecular Infection Biology, University of Würzburg, 97080 Würzburg, Germany.
Malvika
M
Sharan
Department of Microbiology, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
Vera
V
Kozjak-Pavlovic
Institute for Molecular Infection Biology, University of Würzburg, 97080 Würzburg, Germany.
Ana
0000-0002-7355-0674
A
Eulalio
Department of Microbiology, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
Bhupesh K
0000-0001-7051-4670
BK
Prusty
Department of Microbiology, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
Martin
0000-0002-4581-6244
M
Fraunholz
Department of Microbiology, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
Karthika
K
Karunakaran
Department of Microbiology, Biocenter, University of Würzburg, 97074 Würzburg, Germany thomas.rudel@biozentrum.uni-wuerzburg.de.
Thomas
0000-0003-4740-6991
T
Rudel
D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008928:Mitochondria / Q000382:microbiology*; D063154:Mitochondrial Dynamics / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
D035683:MicroRNAs