Role of Type 4B Secretion System Protein, IcmE, in the Pathogenesis of Coxiella burnetii
| dc.contributor.author | Palanisamy, Rajesh | |
| dc.contributor.author | Zhang, Yan | |
| dc.contributor.author | Zhang, Guoquan | |
| dc.date.accessioned | 2024-06-28T15:31:50Z | |
| dc.date.available | 2024-06-28T15:31:50Z | |
| dc.date.issued | 2024-05-14 | |
| dc.date.updated | 2024-06-28T15:31:50Z | |
| dc.description.abstract | <i>Coxiella burnetii</i> is an obligate intracellular Gram-negative bacterium that causes Q fever, a life-threatening zoonotic disease. <i>C. burnetii</i> replicates within an acidified parasitophorous vacuole derived from the host lysosome. The ability of <i>C. burnetii</i> to replicate and achieve successful intracellular life in the cell cytosol is vastly dependent on the Dot/Icm type 4B secretion system (T4SSB). Although several T4SSB effector proteins have been shown to be important for <i>C. burnetii</i> virulence and intracellular replication, the role of the icmE protein in the host–<i>C. burnetii</i> interaction has not been investigated. In this study, we generated a <i>C. burnetii</i> Nine Mile Phase II (NMII) mutant library and identified 146 transposon mutants with a single transposon insertion. Transposon mutagenesis screening revealed that disruption of <i>icmE</i> gene resulted in the attenuation of <i>C. burnetii</i> NMII virulence in SCID mice. ELISA analysis indicated that the levels of pro-inflammatory cytokines, including interleukin-1β, IFN-γ, TNF-α, and IL-12p70, in serum from Tn::icmE mutant-infected SCID mice were significantly lower than those in serum from wild-type (WT) NMII-infected mice. Additionally, Tn::icmE mutant bacteria were unable to replicate in mouse bone marrow-derived macrophages (MBMDM) and human macrophage-like cells (THP-1). Immunoblotting results showed that the Tn::icmE mutant failed to activate inflammasome components such as IL-1β, caspase 1, and gasdermin-D in THP-1 macrophages. Collectively, these results suggest that the icmE protein may play a vital role in <i>C. burnetii</i> virulence, intracellular replication, and activation of inflammasome mediators during NMII infection. | |
| dc.description.department | Molecular Microbiology and Immunology | |
| dc.identifier | doi: 10.3390/pathogens13050405 | |
| dc.identifier.citation | Pathogens 13 (5): 405 (2024) | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12588/6487 | |
| dc.publisher | MDPI | |
| dc.rights | Attribution 4.0 United States | |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
| dc.title | Role of Type 4B Secretion System Protein, IcmE, in the Pathogenesis of Coxiella burnetii | |
| dc.type | Article |