Journal
FRONTIERS IN MICROBIOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2019.00042
Keywords
antibiotic resistance; selection; Staphylococcus epidermidis; repeatability; replication
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Funding
- UCLA Department of Ecology and Evolutionary Biology
- UCLA David Geffen School of Medicine
- Hellman Foundation through the NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI grant [UL1TR001881]
- KL2 Fellowship through the NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI grant [UL1TR001881]
- National Institutes of Health, under Ruth L. Kirschstein National Research Service Award [T32-GM008185]
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Objectives: Understanding how phenotypic traits vary has been a longstanding goal of evolutionary biologists. When examining antibiotic-resistance in bacteria, it is generally understood that the minimum inhibitory concentration (MIC) has minimal variation specific to each bacterial strain-antibiotic combination. However, there is a less studied resistance trait, the mutant prevention concentration (MPC), which measures the MIC of the most resistant sub-population. Whether and how MPC varies has been poorly understood. Here, we ask a simple, yet important question: How much does the MPC vary, within a single strain-antibiotic association? Using a Staphylococcus species and five antibiotics from five different antibiotic classes-ciprofloxacin, doxycycline, gentamicin, nitrofurantoin, and oxacillin-we examined the frequency of resistance for a wide range of concentrations per antibiotic, and measured the repeatability of the MPC, the lowest amount of antibiotic that would ensure no surviving cells in a 1010 population of bacteria. Results: We found a wide variation within the MPC and distributions that were rarely normal. When antibiotic resistance evolved, the distribution of the MPC changed, with all distributions becoming wider and some multi-modal. Conclusion: Unlike the MIC, there is high variability in the MPC for a given bacterial strain-antibiotic combination.
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