Tolerant Coxiella burnetii survives doxycycline stress: Proteomics reveals crucial mechanisms

Coxiella burnetii is an intracellular pathogen that causes Q fever, a zoonotic disease found worldwide. In humans, the bacterium is responsible for an acute and chronic disease. It is transmitted to humans by the inhalation of aerosols or contaminated dust containing bacteria from infected livestock. Recently C. burnetii re-emerged in Europe making considerable economic impact in farming industry and even causing multiple human cases. Antibiotic resistance represents a global public health problem; moreover, there are few reports about doxycycline resistance in C. burnetii. Understanding drug application consequences in tolerant bacterial strains is indispensable for the effective therapy. Herein, we report changes in proteome of C. burnetii challenged by antibiotic stress, highlighting polypeptides likely involved in the detoxification of doxycycline. These data were corroborated by gene expression analysis. Based on the identities of differentially abundant proteins we suggest that homeostasis of bacterial surface, oxidative stress defense and balanced carbon metabolism are key processes to survive doxycycline treatment.