A mutation in Escherichia coli ftsZ bypasses the requirement for the essential division gene zipA and confers resistance to FtsZ assembly inhibitors by stabilizing protofilament bundling.

The earliest step in Escherichia coli cell division consists of the assembly of FtsZ protein into a proto-ring structure, tethered to the cytoplasmic membrane by FtsA and ZipA. The proto-ring then recruits additional cell division proteins to form the divisome. Previously we described an ftsZ allele, ftsZL169R , which maps to the side of the FtsZ subunit and confers resistance to FtsZ assembly inhibitory factors including Kil of bacteriophage λ. Here we further characterize this allele and its mechanism of resistance. We found that FtsZL169R permits the bypass of the normally essential ZipA, a property previously observed for FtsA gain-of-function mutants such as FtsA* or increased levels of the FtsA-interacting protein FtsN. Similar to FtsA*, FtsZL169R also can partially suppress thermosensitive mutants of ftsQ or ftsK, which encode additional divisome proteins, and confers strong resistance to excess levels of FtsA, which normally inhibit FtsZ ring function. Additional genetic and biochemical assays provide further evidence that FtsZL169R enhances FtsZ protofilament bundling, thereby conferring resistance to assembly inhibitors and bypassing the normal requirement for ZipA. This work highlights the importance of FtsZ protofilament bundling during cell division and its likely role in regulating additional divisome activities.