Bacterial cell shape determining factors of Campylobacter as potential drug targets

'Campylobacter jejuni' is the most frequent causative agent of enteric diseases in many countries. The lack of vaccines and emergence of multidrug resistant forms necessitates the development of alternative antibacterials targeting this important pathogen. One remarkable feature of this bacterium is its ability to change cells shape from a typically spiral (or rod) form to a coccoid form (CF). Despite some contradictory data, the results of a number of studies suggest that this is a degenerative form of the bacterium. Despite being non-viable, the CFs may play a role of biofilm formation. However, the mechanisms of CF formation remain unclear. In this study we have identified and investigated various putative 'Campylobacter' shape-related genes using site-directed mutagenesis and gene expression assays. The gene selection was partially based on sequence similarity to cell shape-controlling genes found in other bacteria. Surprisingly, in contrast to those bacteria, some of these genes appeared to be essential for 'Campylobacter'. One of these genes was found to be upregulated in conditions stimulating CF formation. In addition, dynamics of CF formation was investigated. The results suggest that this is an active genetically regulated process, and not just a result of bacterial degenerative degradation in unfavourable conditions. The finding therefore supports a possibility to develop novel antibacterial drugs targeting the genes and their products involved in bacterial cell shape changes.