Chemical inhibition of cell surface modification sensitizes bacteria to phage infection

Many bacteriophages that infect Gram-positive bacteria rely on the bacterial cell surface polymer wall teichoic acid (WTA) as a receptor. However, some bacteria modulate their cell wall with d-alanine residues, which can disrupt phage adsorption. The prevalence and significance of WTA alanylation as an anti-phage defense is unknown. A chemical inhibitor of WTA d-alanylation could be employed to efficiently screen phage-host combinations for those that exhibit alanylation-dependent infections. Since the incorporation of d-alanine residues into the cell wall requires the activity of d-alanine:alanyl carrier protein ligase (DltA), a DltA inhibitor was employed as this tool. Herein, we found that a chemical probe inhibiting DltA activity impeded bacterial cell wall alanylation and enhanced infectivity of many phages against