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CD31-positive vessel density and Ki-67-positive cell density were determined by analysis of sections from at least 4 independent mice from each genotype.

The Monod half-saturation constant (K s ) was determined by analysis of substrate concentrations at different dilution rates using the Monod equation.

The intra-day precision was determined by analysis of the standard solution at six times within 1 day.

The equilibrium dissociation constant (KD) was determined by analysis of the sensorgram-curves obtained at different concentrations of SB by use of BIA evaluation software version 3.1 (Biacore) and the 1 1 Langmuir binding fitting model.

The KD= Koff/ Kon (where, KD=equilibrium dissociation constant, Kon=association rate constant and Koff=dissociation rate constant) were determined by analysis of the sensorgram curves obtained at different concentrations of WB by use of BIA evaluation v4.1 (Biacore).

The DNA content of each sample was determined by spectrophotometric analysis at 260/280 nm and stored at -80°C until use.

Their affinities were determined by Biacore analysis at the elevated temperature of 35°C due to the slow dissociation rate at 25°C.

e, Heat map showing the mean abundance of all significant modules as determined by MaAsLin analysis at each of the first three time points.

The amount of the released vancomycin hydrochloride was determined by UV analysis at 280 nm (Spectrophotometer UV-160A, Shimadzu, Japan).

Significance of QTL is indicated by LOD score above the threshold values determined by permutation analysis at a significant level of P < 0.05.

Complementation was determined by phenotypic analysis at 37°C in LB plus appropriate antibiotics as described above.