Purine and pyrimidine synthesis differently affect the strength of the inoculum effect for aminoglycoside and β-lactam antibiotics.

ABSTRACT: The inoculum effect has been observed for nearly all antibiotics and bacterial species. However, explanations accounting for its occurrence and strength are lacking. Previous work found that the relationship between [ATP] and growth rate can account for the strength and occurrence of the inoculum effect for bactericidal antibiotics. However, the molecular pathway(s) underlying this relationship, and therefore determining the inoculum effect, remain undiscovered. Using a combination of flux balance analysis and experimentation, we show that nucleotide synthesis can determine the relationship between [ATP] and growth and thus the strength of inoculum effect in an antibiotic class-dependent manner. If the [ATP]/growth rate is sufficiently high as determined by exogenously supplied nitrogenous

SUBMITTER: Hernandez DM 

PROVIDER: S-EPMC11619438 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature