Genetic basis of glycine and L-serine toxicity in Staphylococcus aureus and the case for glycine as an antibiotic adjuvant.

Transposon insertion sequencing in Staphylococcus aureus identifies alanine counterbalancing and specific uptake transporters as key mechanisms enabling tolerance to excess glycine, L-serine, and diglycine.

• Why it matters: Excess glycine and L-serine can inhibit bacterial growth, but the genetic basis of tolerance—and how to exploit it for combination therapy—was unclear.
• What they did: Tn-seq mapped genes required for fitness under excess L-serine, diglycine, or glycine, highlighting DtpT for L-serine or glycine, AapA for diglycine, and TcyABC for excess L-serine.
• The result: Glycine and diglycine toxicity is neutralized by Dat-dependent D-alanine synthesis, and combined glycine plus D-cycloserine is strongly synergistic in inhibiting S. aureus growth.