Towards novel antibacterial strategies
Bacteria modulate their growth to become stationary and thus resist environmental stress. Biofilm formation is a result of such stress conditions. The EU-funded 'Studies on the bacterial stress response and stress-induced cross-resistance' (BACTERIAL STRESS) project worked to characterise the molecular mechanisms responsible for stress-induced resistance in the Gram negative bacterium Escherichia coli. Previous work by the BACTERIAL STRESS scientists had implicated the ribosome in stress-induced resistance. In particular, they identified certain kasugamycin-resistance (ksgr) mutations that affected 16S ribosomal RNA (rRNA) and caused abnormal bacterial growth at low temperature. Experiments showed that for cross-resistance to develop, ksgr mutant bacteria had to pass through the stationary phase. This necessitated genome-wide analysis to understand the genetic changes involved in the bacterial stress response when bacteria slow down their growth. In parallel, scientists focused on the development of novel antibacterial compounds against iron scavenging. The rationale was that understanding the structural details of the interaction between siderophore and their outer-membrane receptors would lead to a better antibacterial design. The work concentrated on siderophore synthesis and receptor crystallisation in the photobacterium damselae piscicida, the causative agent of the marine fish disease pasteurellosis or photobacteriosis. Scientists successfully isolated and characterised the siderophore piscibactin and set out to design compounds against the activity of this iron-chelating molecule. A significant amount of BACTERIAL STRESS activities were devoted to mutations in the mitochondrially-encoded rRNA (mt-rRNA) genes and their role in disease pathogenesis. Researchers developed a novel analytical method for studying previously uncharacterised mutations and identified many sequence variations. Some of these were predicted to be pathogenic causing a deficient translational apparatus in the mitochondria of the affected tissues. This part of the work has the potential to lead to novel diagnostic tools for mitochondrial diseases.
Keywords
Epidemiology, virulence, bacteria, stress-induced cross-resistance, ksgr mutations, siderophore, mitochondrial rRNA