| dc.description.abstract | The nucleus is the brain of the cell and is the site of regulation of processes such as DNA replication, transcription and cell cycle. Given its importance in cell function, several known bacterial proteins have been shown to modulate nuclear processes to coopt the host cell for the benefit of the bacteria. Such proteins, termed nucleomodulins, can modulate either nuclear DNA or proteins through a variety of mechanisms. Coxiella burnetii is a Gram negative, obligate intracellular pathogen and the etiological agent of the zoonotic disease known as Q fever. The goal of this project is to determine if C. burnetii employs any of its type IVB secretion system (T4SS) substrates to act as nucleomodulins. In a large-scale screen of T4BSS substrates, we showed six substrates that exhibited nuclear localization when expressed ectopically in HeLa cells. Bioinformatic analysis revealed that two of these potential Nucleomodulins, CBU0388 and CBU0794, contained potential nuclear localization signals (NLS).
We tested the functionality of these regions by making specific amino acid deletions and comparing the impact on their nuclear localization patterns. To predict functionality of these substrates, we conducted an Epistasis Miniarray profile (EMAP) screen in S. cerevisiae which provided a global quantitative genetic profile of host interactions. Our results support our hypothesis these two previously uncharacterized C. burnetii substrates act uniquely as nucleomodulins in the host cell. | en |
