Abstract
Antibiotic resistance is ancient and widespread in environmental bacteria. These are therefore reservoirs of resistance elements and reflective of the natural history of antibiotics and resistance. In a previous study, we discovered that multi-drug resistance is common in bacteria isolated from Lechuguilla Cave, an underground ecosystem that has been isolated from the surface for over 4 Myr. Here we use whole-genome sequencing, functional genomics and biochemical assays to reveal the intrinsic resistome of Paenibacillus sp. LC231, a cave bacterial isolate that is resistant to most clinically used antibiotics. We systematically link resistance phenotype to genotype and in doing so, identify 18 chromosomal resistance elements, including five determinants without characterized homologues and three mechanisms not previously shown to be involved in antibiotic resistance. A resistome comparison across related surface Paenibacillus affirms the conservation of resistance over millions of years and establishes the longevity of these genes in this genus.
Highlights
Antibiotic resistance is ancient and widespread in environmental bacteria
Studies over the past decade have revealed that antibiotic resistance is common in contemporary and ancient environmental bacteria, and that the associated genes are similar or identical to those circulating in pathogens[1]
This is consistent with surveys of modern non-pathogenic environmental bacteria and metagenomes that show that the antibiotic resistome, the collection of all antibiotic resistance elements, is extensive in the microbial world, as well as genetically and mechanistically varied[4,5,6,7,8]
Summary
Antibiotic resistance is ancient and widespread in environmental bacteria. These are reservoirs of resistance elements and reflective of the natural history of antibiotics and resistance. We discovered that multi-drug resistance is common in bacteria isolated from Lechuguilla Cave, an underground ecosystem that has been isolated from the surface for over 4 Myr. Here we use whole-genome sequencing, functional genomics and biochemical assays to reveal the intrinsic resistome of Paenibacillus sp. The result is a comprehensive analysis of resistance genotype and phenotype from a bacterial strain isolated geologically and temporally from contemporary surface members of the same genus and species We report both a remarkable conservation of resistance mechanisms over millions of years and the discovery of five new resistance elements that we realize are widespread in the environment and potential sources of clinical concern should they be mobilized into pathogens. LC231 and determined that in addition to resistance to 14 classes of antibiotic, it inactivates 7 distinct classes
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