Coxiella burnetii Nine Mile II proteins modulate gene expression of monocytic host cells during infection

BMC Microbiology

Research Article

Patricia Ayoubi¹  Saugata Mahapatra²  Edward I Shaw² 

[1] Department of Biochemistry and Molecular Biology, Oklahoma State University, 246C Noble Research Center, 74078, Stillwater, OK, USA;Department of Microbiology and Molecular Genetics, Oklahoma State University, 307 Life Sciences East, 74078, Stillwater, OK, USA;

关键词: Host Gene;    Ingenuity Pathway Analysis;    Parasitophorous Vacoule;    Coxiella Burnetii;    Bacterial Protein Synthesis;   

DOI  :  10.1186/1471-2180-10-244

 received in 2010-06-30, accepted in 2010-09-20,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundCoxiella burnetii is an intracellular bacterial pathogen that causes acute and chronic disease in humans. Bacterial replication occurs within enlarged parasitophorous vacuoles (PV) of eukaryotic cells, the biogenesis and maintenance of which is dependent on C. burnetii protein synthesis. These observations suggest that C. burnetii actively subverts host cell processes, however little is known about the cellular biology mechanisms manipulated by the pathogen during infection. Here, we examined host cell gene expression changes specifically induced by C. burnetii proteins during infection.ResultsWe have identified 36 host cell genes that are specifically regulated when de novoC. burnetii protein synthesis occurs during infection using comparative microarray analysis. Two parallel sets of infected and uninfected THP-1 cells were grown for 48 h followed by the addition of chloramphenicol (CAM) to 10 μg/ml in one set. Total RNA was harvested at 72 hpi from all conditions, and microarrays performed using Phalanx Human OneArray™ slides. A total of 784 (mock treated) and 901 (CAM treated) THP-1 genes were up or down regulated ≥2 fold in the C. burnetii infected vs. uninfected cell sets, respectively. Comparisons between the complementary data sets (using >0 fold), eliminated the common gene expression changes. A stringent comparison (≥2 fold) between the separate microarrays revealed 36 host cell genes modulated by C. burnetii protein synthesis. Ontological analysis of these genes identified the innate immune response, cell death and proliferation, vesicle trafficking and development, lipid homeostasis, and cytoskeletal organization as predominant cellular functions modulated by C. burnetii protein synthesis.ConclusionsCollectively, these data indicate that C. burnetii proteins actively regulate the expression of specific host cell genes and pathways. This is in addition to host cell genes that respond to the presence of the pathogen whether or not it is actively synthesizing proteins. These findings indicate that C. burnetii modulates the host cell gene expression to avoid the immune response, preserve the host cell from death, and direct the development and maintenance of a replicative PV by controlling vesicle formation and trafficking within the host cell during infection.

【 授权许可】

Unknown   
© Mahapatra et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.