Novel inhibitors of bacterial cytokinesis identified by a cell-based antibiotic screening assay.

The continuous emergence of antibiotic resistance demands that novel classes of antibiotics continue to be developed. The division machinery of bacteria is an attractive target because it comprises seven or more essential proteins that are conserved almost throughout the bacteria but are absent from humans. We describe the development of a cell-based assay for inhibitors of cell division and its use to isolate a new inhibitor of FtsZ protein, a key player in the division machinery. Biochemical, cytological, and genetic data are presented that demonstrate that FtsZ is the specific target for the compound. We also describe the effects of more potent analogues of the original hit compound that act on important pathogens, again at the level of cell division. The assay and the compounds have the potential to provide novel antibiotics with no pool of pre-existing resistance. They have provided new insight into cytokinesis in bacteria and offer important reagents for further studies of the cell division machinery.

A 28 kbp segment from the spoVM region of the Bacillus subtilis 168 genome.

The sequence of a 28 kbp segment of DNA surrounding the spoVM gene of Bacillus subtilis 168 (lying at approximately 145 degrees on the standard genetic map) has been determined. The region contains 27 ORFs, a number of which have predicted products significantly similar to proteins in sequence databases, particularly to proteins involved in macromolecular synthesis of nucleic acids, proteins and phospholipids. A pair of closely linked genes encode a likely serine protein phosphatase and a serine protein kinase, respectively. Such proteins play important regulatory roles in eukaryotic cells but are rare in prokaryotes.