The Putative Hydrolase YycJ (WalJ) Affects the Coordination of Cell Division with DNA Replication in Bacillus subtilis and May Play a Conserved Role in Cell Wall Metabolism†

Bacteria must accurately replicate and segregate their genetic information to ensure the production of viable daughter cells. The high fidelity of chromosome partitioning is achieved through mechanisms that coordinate cell division with DNA replication. We report that YycJ (WalJ), a predicted member of the metallo--lactamase superfamily found in most low-GC Gram-positive bacteria, contributes to the fidelity of cell division in Bacillus subtilis. B. subtilis walJ (walJBsu) mutants divide over unsegregated chromosomes more frequently than wild-type cells, and this phenotype is exacerbated when DNA replication is inhibited. Two lines of evidence suggest that WalJBsu and its ortholog in the Gram-positive pathogen Streptococcus pneumoniae, WalJSpn (VicX), play a role in cell wall metabolism: (i) strains of B. subtilis and S. pneumoniae lacking walJ exhibit increased sensitivity to a narrow spectrum of cephalosporin antibiotics, and (ii) reducing the expression of a two-component system that regulates genes involved in cell wall metabolism, WalRK (YycFG), renders walJ essential for growth in B. subtilis, as observed previously with S. pneumoniae. Together, these results suggest that the enzymatic activity of WalJ directly or indirectly affects cell wall metabolism and is required for accurate coordination of cell division with DNA replication. All cells are faced with the fundamental challenge of dupli-cating their genetic information and accurately partitioning