AUTHOR=Gianvecchio Crystal , Lozano Natalie Ann , Henderson Claire , Kalhori Pooneh , Bullivant Austin , Valencia Alondra , Su Lauren , Bello Gladys , Wong Michele , Cook Emoni , Fuller Lakhia , Neal Jerome B. , Yeh Pamela J. 

TITLE=Variation in Mutant Prevention Concentrations

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00042

DOI=10.3389/fmicb.2019.00042

ISSN=1664-302X

ABSTRACT=<p><bold>Objectives:</bold>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 <italic>Staphylococcus</italic> 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 10<sup>10</sup> population of bacteria.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusion:</bold> Unlike the MIC, there is high variability in the MPC for a given bacterial strain-antibiotic combination.</p>