Functional Mapping of Phenotypic Plasticity of Staphylococcus aureus Under Vancomycin Pressure

Phenotypic plasticity is the exhibition of various phenotypic traits produced by a single genotype in response to environmental changes, enabling organisms to adapt to environmental changes by maintaining growth and reproduction. Despite its significance in evolutionary studies, we still know little about the genetic control of phenotypic plasticity. In this study, we designed and conducted a genome-wide association study (GWAS) to reveal genetic architecture of how Staphylococcus aureus strains respond to increasing concentrations of vancomycin (0, 2, 4, and 6 μg/mL) in a time course. We implemented functional mapping, a dynamic model for genetic mapping using longitudinal data, to map specific loci that mediate the growth trajectories of abundance of vancomycin-exposed S. aureus strains. 78 significant single nucleotide polymorphisms were identified following analysis of the whole growth and development process, and seven genes might play a pivotal role in governing phenotypic plasticity to the pressure of vancomycin. These seven genes, SAOUHSC_00020 (walR), SAOUHSC_00176, SAOUHSC_00544 (sdrC), SAOUHSC_02998, SAOUHSC_00025, SAOUHSC_00169, and SAOUHSC_02023, were found to help S. aureus regulate antibiotic pressure. Our dynamic gene mapping technique provides a tool for dissecting the phenotypic plasticity mechanisms of S. aureus under vancomycin pressure, emphasizing the feasibility and potential of functional mapping in the study of bacterial phenotypic plasticity.