Search for: All records

Coxiella burnetii is an obligate intracellular bacterium that lives in a modified lysosome termed the Coxiella containing vacuole (CCV). C. burnetii is the causative agent of the zoonotic illness Q Fever, which primarily infects ruminant livestock and can spread to humans via inhalation. Acute Q fever is characterized by a flu like illness, while chronic disease is associated with more severe symptoms including endocarditis and chronic fatigue syndrome. C. burnetii has a biphasic life cycle consisting of a small cell variant (SCV) and large cell variant (LCV). The SCV is environmentally stable and can cause infection via inhalation of 1 - 10 infectious particles. Once taken up by the host cell, C. burnetii must manipulate the signaling pathways of the host cell to form the CCV where it switches to the LCV, the metabolic and replicative form of the bacterium. It primarily accomplishes this goal by utilizing a Type IV B Secretion System (T4BSS), which is unique to C. burnetii and Legionella pneumophila. The T4BSS, along with some other secretion mechanisms, secretes effector proteins into the host cell. These proteins then interfere with or modulate the host cell to recruit vacuoles, evade detection by the immune system, and prevent the host cell from initiating apoptosis. After about 6 days, the LCV will convert to SCV and then initiate host cell lysis to spread infection. This review looked at many eukaryotic cells signaling pathways and the interactions between C. burnetii and host proteins. These interactions are responsible for the modulation of host cell pathways necessary for CCV formation and C. burnetii survival. Understanding these interactions better will help with future treatments for C. burnetii infection. Further discoveries in these interactions are crucial for the future of C. burnetii research. 

Abstract Coxiella burnetii (Cb) is an obligate intracellular pathogen in nature and the causative agent of acute Q fever as well as chronic diseases. In an effort to identify genes and proteins crucial to their normal intracellular growth lifestyle, we applied a ‘reverse evolution’ approach where the avirulent Nine Mile Phase II strain of Cb was grown for 67 passages in chemically defined ACCM-D media and gene expression patterns and genome integrity from various passages was compared to passage number one following intracellular growth. Transcriptomic analysis identified a marked downregulation of the structural components of the type 4B secretion system (T4BSS), the general secretory (Sec) pathway, as well as 14 out of 118 previously identified genes encoding effector proteins. Additional downregulated pathogenicity determinants genes included several chaperones, LPS, and peptidoglycan biosynthesis. A general marked downregulation of central metabolic pathways was also observed, which was balanced by a marked upregulation of genes encoding transporters. This pattern reflected the richness of the media and diminishing anabolic, and ATP-generation needs. Finally, genomic sequencing and comparative genomic analysis demonstrated an extremely low level of mutation across passages, despite the observed Cb gene expression changes following acclimation to axenic media.