Phenotypic Plasticity of Staphylococcus aureus in Liquid Medium Containing Vancomycin

Phenotypic plasticity enables individuals to develop different phenotypes in a changing environment and promotes adaptive evolution. Genome-wide association study (GWAS) facilitates the study of the genetic basis of bacterial phenotypes, and provides a new opportunity for bacterial phenotypic plasticity research. To investigate the relationship between growth plasticity and genotype in bacteria, 41 Staphylococcus aureus strains, including 29 vancomycin-intermediate S. aureus (VISA) strains, were inoculated in the absence or presence of vancomycin for 48 h. Growth curves and maximum growth rates revealed that strains with the same minimum inhibitory concentration (MIC) showed different levels of plasticity in response to vancomycin. A bivariate GWAS was performed to map single-nucleotide polymorphisms (SNPs) associated with growth plasticity. In total, 227 SNPs were identified from 14 time points, while 15 high-frequency SNPs were mapped to different annotated genes. The P-values and growth variations between the two cultures suggest that non-coding region (SNP 738836), ebh (SNP 1394043), drug transporter (SNP 264897), and pepV (SNP 1775112) play important roles in the growth plasticity of S. aureus. Our study provides an alternative strategy for dissecting the adaptive growth of S. aureus in vancomycin and highlights the feasibility of bivariate GWAS in bacterial phenotypic plasticity research.