Q-fever

Coxiella burnetii is the causative agent of Q fever which can lead to either acute or chronic infection in humans. Acute Q fever is associated with inflammation, hepatitis and pneumonia. Chronic Q fever, defined as a cardiovascular chronic infection, develops over several months to years following an initial infection and is characterized primarily by endocarditis or endovascular infection. Even though only a small proportion (2-5%) of the infected individuals develops chronic Q fever, the burden for patients is significant, as long-term antimicrobial drug treatment with antibiotics is necessary and mortality can reach to more than 60% when left untreated. The current use of antibiotics to cure Q fever patients that are infected with one single pathogen, C. burnetii, is reminiscent to cancer chemotherapy: in both cases the entire body is exposed to the drug whereas only a relatively small population of cells (cancer cell/bacteria) is the target. In the case of cancers this results in severe side effects for the patient, in the case of Q fever the long term treatment (up to 4 years) does not only have significant side effects for the patient but there is also collateral damage of antibiotic use: it contributes to the problematic rise in antibiotic resistance that we are witnessing worldwide 3. In either case, more potent medicines that specifically target the culprits are desirable. Our aim is to generate more specific and potent antibiotics to treat acute and chronic Q fever. Recently it has been shown that the conjugation of antibiotics instead of anti-cancer drugs to antibodies hold great promise for the treatment of multi-drug resistant Staphylococcus aureus(MRSA). Antibiotic antibody conjugates (AAC) have the potential to deliver more potent antibiotics to the site of infection, on one hand increasing elimination of the Q fever causing agent C. burnetii, and on the other hand reducing exposure of the the patient’s commensal bacteria to the antibiotics to prevent accumulation of antibiotics resistance genes.