Data from: Growth productivity as a determinant of the inoculum effect for bactericidal antibiotics
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Dec 14, 2022 version files 994.54 KB
Abstract
Understanding the mechanisms by which populations of bacteria resist antibiotics has implications for evolution, microbial ecology, and public health. The inoculum effect (IE), where antibiotic efficacy declines as the density of a bacterial population increases, has been observed for multiple bacterial species and antibiotics. Several mechanisms to account for IE have been proposed, but most lack experimental evidence or cannot explain IE for multiple antibiotics. We show that growth productivity, the combined effect of growth and metabolism, can account for IE for multiple bactericidal antibiotics and bacterial species. Guided by flux balance analysis and whole genome modeling, we show that the carbon source supplied in the growth medium determines growth productivity. If growth productivity is sufficiently high, IE is eliminated. Our results may lead to approaches to reduce IE in the clinic, help standardize the analysis of new antibiotics, and further our understanding of how bacteria evolve resistance.