Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 65, Issue 10, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00891-21
Keywords
Bacillus subtilis; DNA damage; antibiotic resistance; competition; drug resistance evolution; environmental stressors; mutagenesis; mutational spectrum; selection; spectinomycin
Categories
Funding
- National Institutes of Health from the National Institute of General Medical Sciences [P20GM121344]
- National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [R01DK125382]
- National Science Foundation [1644760]
- Direct For Education and Human Resources
- Division Of Graduate Education [1644760] Funding Source: National Science Foundation
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Research using high-throughput sequencing analyzed the impact of mutations induced by different stressors on bacteria, revealing specific spectra of antibiotic-resistance mutations induced by each stressor. Competitive fitness experiments with multiple strains were used to determine the relative fitness of these mutants under different antibiotic selection pressures.
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.
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