Characterization of Deoxycholate-Responsive Genes Utilized by  Brucella abortus 2308 During Oral Infection

Brucellosis is a chronic, recurring disease caused by the bacterium Brucella abortus, along with other species of the genus Brucella, and is one of the most common bacterial zoonosis worldwide. The bacteria preferentially infect and reside within host macrophages, causing an undulant fever, joint pain, and other flu-like symptoms, in addition to more severe problems like hepatosplenomegaly and endocarditis. Brucella infection is most often acquired via inhalation through the respiratory route, or via consumption of unpasteurized dairy products. Although ingestion is a major route of infection, the transcriptional response of B. abortus during oral infection remains poorly characterized. In this project, RNA sequencing was used to discover genes with the greatest transcriptional changes in B. abortus subjected to deoxycholate, a host bile acid encountered by bacteria during oral infection. Gene deletion strains of B. abortus were then created and tested for susceptibility to pH and bile acid stress, along with their ability to invade and replicate within macrophages. If the genes of interest are important for the oral infection process, B. abortus strains lacking these genes will likely be more susceptible to pH and deoxycholate stress and may exhibit attenuation in the macrophage infection model. Determination of genes important for the oral infection process would further elucidate the molecular mechanisms by which B. abortus invades the host, and could help lead to future treatments and novel therapeutics.