The soil microbiome can produce, resist, or degrade antibiotics and even catabolize them. Resistance genes are widely distributed in the soil and may act as a reservoir for pathogen antibiotic resistance. Work done in the Dantas lab has identified high diversity of genes encoding antibiotic resistance across all antibiotic classes, but generally these genes are not at great risk of mobilization to pathogens. However, the sub-group of resistant, culturable Proteobacteria show both resistance to high concentrations of antibiotics and resistance across many antibiotic classes. These highly resistant Proteobacteria are related to human pathogens, and show evidence of increased horizontal gene transfer of resistance genes. Interestingly, many of these Proteobacteria are not only antibiotic resistant, they have also been found to be capable of antibiotic catabolism. Little is known about the enzymes, mechanisms, and pathways involved in antibiotic catabolism. We describe a pathway for penicillin catabolism in four strains of Proteobacteria. Genomic and transcriptomic sequencing revealed β -lactamase, amidase, and phenylacetic acid catabolon upregulation. Knocking out part of the phenylacetic acid catabolon or an apparent penicillin utilization operon (put) resulted in loss of penicillin catabolism in one isolate. A hydrolase from the put operon was found to degrade in vitro benzylpenicilloic acid, the β -lactamase penicillin product. To test the generality of this strategy, an Escherichia coli strain was engineered to co-express a β -lactamase and a penicillin amidase or the put operon, enabling it to grow using penicillin or benzylpenicilloic acid, respectively. Elucidation of additional pathways may allow bioremediation of antibiotic-contaminated soils and discovery of antibiotic-remodeling enzymes with industrial utility.

Learning Objectives: 

1. Antibiotics and pharmaceuticals are not privileged molecules, they can be modified or catabolized by microbes. 
2. Metabolism of these molecules in unexpected ways can impact human health.