TABLE 3

Characteristics of double mutants selected for higher-level resistance on plates vs. batch-culture-evolved equivalents

Test
straina
rpoB genotypeReference
straina
rpoB
genotype
Relative
fitness of
test strainb
IC50
test
strainc
IC50
reference
strainc
ER-rif-2AL511Q/D516GK12Wild type101.4 (0.5)377.5 (7.5)6.0 (1.0)
ER-rif-2AL511Q/D516Grif-9D516G99.4 (0.7)144.6 (13)
R200-rif-2L511Q/D516GK12Wild type101.5 (1.2)387.5 (7.5)
R200-rif-2L511Q/D516Grif-9D516G97.6 (1.2)
R800-rif-2L511Q/D516GK12Wild type101.4 (1.1)390.0 (20)
R800-rif-2L511Q/D516Grif-9D516G97.8 (1.5)
  • a Relative fitness was determined via direct competition between a test strain carrying a neutral marker ([mal]) and an unmarked reference strain. (R200-rif-2 and R800-rif-2 are plate-evolved mutants; ER-rif-2A is a culture-evolved mutant.)

  • b See Table 1 legend for details of relative fitness determination.

  • c IC50 values indicate the concentration of rifampin (in micrograms/milliliters) at which the rate of bacterial growth is 50% maximal for a given strain. The value in parentheses is the standard error of the IC50 based on two to three independent determinations. The IC50 for rif-2 (L511Q) is 28.6 (±1.0).