The stringent starvation protein SspA modulates peptidoglycan synthesis by regulating the expression of peptidoglycan synthases.

The peptidoglycan (PG) layer of bacterial cells is essential for maintaining the cell shape and survival of cells; therefore, the synthesis of PG needs to be spatiotemporally controlled. While it is well established that PG synthesis is mediated posttranslationally through interactions between PG synthases and their cognate partners, much less is known about the transcriptional regulation of genes encoding these synthases. Based on a previous finding that the Gram-negative bacterium Shewanella oneidensis lacking the prominent PG synthase exhibits impaired cell wall integrity, we performed genetic selections to isolate the suppressors. We discovered that disrupting the sspA gene encoding stringent starvation protein A (SspA) is sufficient to suppress compromised PG. SspA serves as a transcriptional repressor that regulates the expression of the two types of PG synthases, class A penicillin-binding proteins and SEDS/bPBP protein complexes. SspA is an RNA polymerase-associated protein, and its regulation involves interactions with the σ 70 -RNAP complex and an antagonistic effect of H-NS, a global nucleoid-associated protein. We also present evidence that the regulation of PG synthases by SspA is conserved in Escherichia coli, adding a new dimension to the current understanding of PG synthesis and its regulation.