Wall teichoic acids regulate peptidoglycan synthesis by paving cell wall nanostructure

The bacterial cell wall is a polymeric exoskeleton, composed largely of peptidoglycan, that determines cell size and shape. Two systems synthesize peptidoglycan during the growth of rod-shaped bacteria, which are found pervasively across diverse bacterial taxa: the multi-protein Rod complexes are critical for cell shape because they synthesize anisotropic peptidoglycan oriented along the cell circumference^1-3, whereas PBP1 synthesizes isotropic peptidoglycan^1,4 (Fig. 1A). In Gram-positive bacteria, rod shape is also dependent on wall teichoic acids⁵, an abundant cell wall polymer, for entirely unknown reasons. Here, we show that teichoic acids occlude nanoscopic pores in the cell wall, which simultaneously promotes Rod complex activity and inhibits PBP1. Depletion of teichoic acids exposed these pores within minutes, coinciding with a rapid activation of PBP1. In contrast to previous steady-state measurements^6,7, we found that teichoic acid depletion also caused the transient arrest of Rod complexes prior to the onset of amorphous growth. Teichoic acids, therefore, are a new critical factor in peptidoglycan synthesis regulation. Our work further identifies the cell wall, via its molecular-scale structure, as a non-canonical auto-regulatory factor in its own synthesis. Since teichoic acids additionally govern peptidoglycan hydrolysis^8-13, our results position these polymers as "master regulators" of rod-shaped cell growth.