Genotoxic Agents Produce Stressor-Specific Spectra of Spectinomycin Resistance Mutations Based on Mechanism of Action and Selection in Bacillus subtilis
| Autor: | Jason T. Machan, Ashley H Choi, Benjamin J. Korry, Peter Belenky, Stella Ye Eun Lee, Collin Ganser, Amit K Chakrabarti |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Spectinomycin
DNA damage Mutant Mutagenesis (molecular biology technique) Bacillus subtilis Biology 03 medical and health sciences chemistry.chemical_compound Mechanisms of Resistance medicine Pharmacology (medical) Gene 030304 developmental biology Pharmacology Genetics 0303 health sciences 030306 microbiology Mechanism (biology) Drug Resistance Microbial biology.organism_classification Anti-Bacterial Agents Infectious Diseases chemistry Mutation DNA medicine.drug DNA Damage |
| Zdroj: | Antimicrob Agents Chemother |
| Popis: | Mutagenesis is integral for bacterial evolution and the development of antibiotic resistance. Environmental toxins and stressors are known to elevate the rate of mutagenesis through direct DNA toxicity, known as stress-associated mutagenesis, or via a more general stress-induced process that relies on intrinsic bacterial pathways. Here, we characterize the spectra of mutations induced by an array of different stressors using high-throughput sequencing to profile thousands of spectinomycin-resistant colonies of Bacillus subtilis. We found 69 unique mutations in the rpsE and rpsB genes, and that each stressor leads to a unique and specific spectrum of antibiotic-resistance mutations. While some mutations clearly reflected the DNA damage mechanism of the stress, others were likely the result of a more general stress-induced mechanism. To determine the relative fitness of these mutants under a range of antibiotic selection pressures, we used multistrain competitive fitness experiments and found an additional landscape of fitness and resistance. The data presented here support the idea that the environment in which the selection is applied (mutagenic stressors that are present), as well as changes in local drug concentration, can significantly alter the path to spectinomycin resistance in B. subtilis. |
| Databáze: | OpenAIRE |
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