Bacteria have developed extensive response systems to survive and prevail in their constantly changing environment. A classic example is the SOS response in which cell division is prevented in response to DNA damage, allowing repair of the DNA prior to its segregation into newborn cells. This continuation of cell growth and DNA replication in the absence division is known as filamentation. Bacterial filamentation is a widely conserved survival response during pathogenesis and exposure to a range of antibiotics. This includes the extensive filamentation that occurs during urinary tract infection by uropathogenic Escherichia coli. With the increase of antibiotic resistances, regulators that enable filamentation are attractive targets for new antibacterials, but remain largely unknown.
A recent screen for filamentation genes identified a candidate novel inhibitor of division in E. coli, ymfM, an SOS-inducible gene of the e14 prophage. Immunofluorescence microscopy of cells induced to overexpress ymfM revealed that its gene product prevents assembly of the cytokinetic ring, called the Z ring. A block in division following DNA damage has traditionally been attributed solely to the SOS-induced protein, SulA, which inhibits FtsZ polymerization, upon activation of its expression by the RecA protein. However, when ymfM is activated by RecA, division inhibition is independent of SulA, suggesting that there are multiple RecA-induced stress responses in E. coli. We are currently deciphering the role of ymfM in stress survival and the mechanism of Z ring inhibition by its product, YmfM. This will allow a clearer understanding of the diverse pathways utilised by E. coli during stress, how this links with cell division regulation, and facilitate the identification of new antibacterial targets.