Antibiotic Minimal Selective Concentrations and Fitness Costs during Biofilm and Planktonic Growth

Abstract

Our understanding of how and where antibiotic resistance is selected in response to antibiotic exposure is still limited, and this is particularly true for selective processes when bacteria are growing in biofilms, arguably the most significant mode of growth of bacteria in human and animal infections as well as in other settings. In this study, we compared how different types of resistant E. coli strains were selected in response to antibiotic exposure during planktonic and biofilm growth.

Biofilm antimicrobial susceptibility through an experimental evolutionary lens

“…Evolved biofilm populations maintain a higher diversity than corresponding planktonic populations, in which successful mutations reach fixation quickly, and the biofilm environment may protect against negative selection of less fit resistant mutants that would be quickly outcompeted in planktonic cultures 121 . However, a recent study indicated that fitness costs for resistance in surfaceassociated E. coli biofilms did not differ from those in planktonic cultures 79 . In addition, another recent study has shown that the specific environment co-determines fitness and resistance levels associated with specific mutations 131 .…”

“…There is no information on which concentration range constitutes the mutant selection window (MSW, Box 1 ) for biofilms and various aspects of biofilm biology likely affect this window 90 , 91 . While it has been predicted that biofilm growth leads to shifts and distortions of the MSW 91 , recent work with E. coli showed that minimal selective concentration values (for five different antibiotics) did not differ between planktonic cultures and biofilms 79 . Due to the uncertainty concerning the biofilm MSW, antibiotic concentrations are often selected based on the MIC 70 or on the minimal biofilm inhibitory concentration 74 .…”

“… Minimal inhibitory concentration (MIC) : lowest concentration of an antibiotic that prevents growth of planktonic cells 31 , 32 . Mutant selection window (MSW) : the concentration range where the fitness of a resistant mutant is higher than the wild type 79 , 91 . Persistence : phenomenon in which at least two subpopulations are present in a population, one consisting of cells that are killed fast by the antibiotic and the other composed of tolerant cells that survive 48 .…”

“…Mutant selection window (MSW) : the concentration range where the fitness of a resistant mutant is higher than the wild type 79 , 91 .…”

“…The resulting cell suspensions can then be used to start biofilm formation on pegs on a new lid 77 . A conceptually-similar system (FlexiPeg) was recently developed and used to study competition and fitness in biofilms 78 , 79 .…”