Daniel Vega Mendoza, William Margolin
ZipA is essential for cell division in Escherichia coli, acting early in the process to anchor polymers of FtsZ to the cytoplasmic membrane. Along with FtsA, FtsZ and ZipA form a proto-ring at midcell that recruits additional proteins to eventually build the division septum. Cells carrying the thermosensitive zipA1 allele divide fairly normally at 30°C in rich medium but cease dividing at temperatures above 34°C, forming long filaments. In a search for suppressors of zipA1, we found that deletions of specific genes involved in amino acid biosynthesis could partially cell rescue growth and division at 34°C or 37°C, but not at 42°C. Notably, although a diverse group of amino acid biosynthetic gene deletions could partially rescue growth of zipA1 cells at 34°C, only deletions of genes related to the biosynthesis of threonine, glycine, serine and methionine could rescue at 37°C. Adding exogenous pyridoxal 5-phosphate (PLP), a cofactor for many of the enzymes affected by this study, partially suppressed zipA1 thermosensitivity. For many of the deletions, PLP had an additive rescuing effect on zipA1 Moreover, added PLP partially suppressed the thermosensitivity of ftsQ and ftsK mutants, weakly suppressed an ftsI mutant, but failed to suppress ftsA or ftsZ thermosensitive mutants. Along with the ability of a deletion of metC to partially suppress ftsK, our results suggest that perturbations of amino acid metabolic pathways, particularly those that redirect the flow of carbon away from synthesis of threonine, glycine, or methionine, are able to partially rescue some cell division defects.IMPORTANCE Cell division of bacteria such as Escherichia coli is essential for their successful colonization. It is becoming increasingly clear that nutritional status and central metabolism can affect bacterial size and shape; for example, a metabolic enzyme (OpgH) can moonlight as a regulator of FtsZ, an essential cell division protein. Here, we demonstrate a link between amino acid metabolism and ZipA, another essential cell division protein that binds directly to FtsZ and tethers it to the cytoplasmic membrane. Our evidence suggests that altering flux through the methionine-threonine-glycine-serine pathways, and supplementing with the enzyme cofactor pyridoxal-5-phosphate, can partially compensate for an otherwise lethal defect in ZipA as well as several other cell division proteins.
