Engineering the human lung microbiome to degrade inhaled carcinogens
Benzene, an inhaled carcinogen linked to leukemia and lymphoma, is found in consumer goods and industrial byproducts. To reduce exposure-related illnesses, we engineered bacteria to degrade benzene into safe metabolites in a nine-enzyme pathway. This prophylactic Benzene REduction THERapy (BREaTHER) may be introduced to the lung microbiome. As proof-of-concept we evaluated the ability of engineered E. coli to degrade benzene via gas chromatography and measured improvements in the benzene tolerance of engineered strains. We also demonstrated that nebulizers can efficiently deliver BREaTHER into the lungs. To define the conditions under which BREaTHER is safe and effective, we developed a mathematical model. We envision BREaTHER using a variety of lung microbes and have designed ‘universal’ promoters and ribosome binding sites via analysis of various Gram positive and negative bacteria. BREaTHER may one day provide additional protection for concerned individuals and reduce the occupational exposure of high risk workers such as firefighters.