@article{Environments:2979,
      recid = {2979},
      author = {Varesio, Lydia Mimi},
      title = {The Response of <i>Brucella ovis</i> to  Changing and Challenging Environments},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2021-06},
      pages = {205},
      abstract = {Bacteria inhabit many environments, from hot dry desert  regions to high pressure niches on the ocean floors, from  high salt areas to cold latitudes, from inside plant root  nodules to inside human cells. Studying the kinds of  habitats different bacteria encounter and how they react to  the challenges these environments offer is important to  understand bacteria in their natural state, what kind of  responses characterize them and how they can function when  confronted with adversity. Here I present my research on  Brucella ovis, a facultative intracellular pathogen that  has evolved to withstand stressful and harmful situations,  from nutrient limitation, to oxidative stress, to drastic  drops in pH. One ambient factor that perturbs B. ovis  homeostasis is the atmospheric level of carbon dioxide, as  B. ovis cannot be cultured in laboratory conditions without  CO2 supplementation. I examined the genetic underpinnings  of the CO2 dependence of B. ovis growth, identifying  mutations in a carbonic anhydrase gene (bcaA) as  responsible for this particular metabolic requirement. B.  ovis harbors a unique, non-functional pseudogene allele of  bcaA (bcaAbov), and I found that some B. abortus lineages  also harbor a bcaA pseudogene, thus rendering them  dependent on CO2 supplementation for growth. My data  explain why B. ovis and select strains of B. abortus  require elevated CO2 levels for growth, which was first  noted over a century ago. Transcription of one third of the  genes in wild-type Brucella ovis change when cells are  shifted from high to low CO2 conditions; gene expression is  unchanged upon CO2 shift in a strain in which the  pseudogene is restored to a functional bcaA. Thus,  wild-type B. ovis has increased sensitivity to  environmental levels of CO2 because of a carbonic anhydrase  pseudogene. This sensitivity could help B. ovis better  detect when it is inside and outside the host.
I also  present work in which I analyze Brucella ovis in the  context of stationary phase, as a proxy to better  understand the environment and related response that this  pathogen encounters within the host. I discovered that cysE  -which encodes for a serine O-acetyltransferase, involved  in the first step of de novo cysteine biosynthesis- is  required for B. ovis fitness in stationary phase. Deletion  of cysE increases sensitivity to hydrogen peroxide and  attenuates Brucella ovis in tissue culture infection  models. Thus, sulfur and cysteine metabolism is important  for resistance to the hostile environment within the  intracellular niche and presents an intriguing target for  drug development against Brucella infections. },
      url = {http://knowledge.uchicago.edu/record/2979},
      doi = {https://doi.org/10.6082/uchicago.2979},
}