The spherical bacterium Staphylococcus aureus, a leading cause of
nosocomial infections, undergoes binary fission by dividing in two alternating orthogonal planes, but the mechanism by which S. aureus correctly selects the next cell division plane is not known. To identify cell division placement factors, we performed a chemical genetic screen that revealed a gene which we termed pcdA. We show that PcdA is a member of the McrB family of AAA+ NTPases that has undergone structural changes and a concomitant functional shift from a restriction
enzyme subunit to an early cell division
protein. PcdA directly interacts with the
tubulin-like central divisome component FtsZ and localizes to future cell division sites before membrane invagination initiates. This parallels the action of another McrB family
protein, CTTNBP2, which stabilizes microtubules in animals. We show that PcdA also interacts with the structural
protein DivIVA and propose that the DivIVA/PcdA complex recruits unpolymerized FtsZ to assemble along the proper cell division plane. Deletion of pcdA conferred abnormal, non-orthogonal division plane selection, increased sensitivity to cell wall-targeting
antibiotics, and reduced virulence in a murine
infection model. Targeting PcdA could therefore highlight a treatment strategy for combatting
antibiotic-resistant strains of S. aureus.