1. Coxiella burnetii control of the host transcription factors TFEB and TFE3
- Author
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Padmanabhan, Bhavna and Padmanabhan, Bhavna
- Abstract
Coxiella burnetii, the etiological agent of the zoonotic disease Q fever, is an obligate Gram-negative intracellular bacterial pathogen that replicates inside the lysosome-derived CCV (Coxiella-containing vacuole) within mammalian hosts. The CCV maintains the degradative and acidic nature of the host lysosome despite C. burnetii directing the massive expansion of this compartment to accommodate the replicating pathogen. To establish this unique replicative niche, C. burnetii requires the Dot/Icm type IV secretion system (T4SS). This T4SS translocates approximately 150 effectors into the host cell to modulate various cellular processes. To date, the functional role of very few of these effectors have been defined. Given the CCV’s origins it is not surprising that C. burnetii infection increases host autophagy and lysosome biogenesis. To investigate this at the protein level, we employed an elegant SILAC based proteome analysis of human cells infected with C. burnetii. This validated that many proteins involved in these processes are increased in abundance during infection. This prompted us to examine the role of the human transcription factor EB (TFEB) and its close homologue TFE3 during C. burnetii infection. TFEB is a master transcription regulator directly controlling the expression of a network of genes responsible for autophagy and lysosome biogenesis. 3 day’s post-infection with C. burnetii, TFEB/TFE3 is activated as demonstrated by TFEB/TFE3 trafficking from the cytoplasm into the nucleus. The nuclear translocation of TFEB/TFE3 appears to be controlled by C. burnetii as blocking bacterial translation with chloramphenicol leads to TFEB/TFE3 movement back into the cytoplasm. siRNA silencing of tfeb and tfe3 additionally demonstrated their contribution towards the intracellular success of C. burnetii. Interestingly, these host factors did not contribute to the replication of C. burnetii but in the absence of TFEB and TFE3 the CCV did not undergo its typical massi
- Published
- 2020