Programmed Cell Death in Bacteria
Programmed cell death (PCD), or apoptosis, is defined as an active process that results in cell suicide and is recognized as an essential mechanism in multicellular organisms where it is required for eliminating superfluous or potentially harmful cells. In bacteria, PCR is mediated through a unique genetic system consisting of a pair of genes that specify two components - a stable toxin, and an unstable antitoxin that prevents the lethal action of the toxin. PCD modules in bacteria were initially found on low-copy-number plasmids or prophages where they are responsible for the death of plasmid-free cells. When the bacteria lose the plasmid (or other extrachromosomal elements), the cured cells are selectively killed because the unstable toxin is degraded faster than the stable toxin. Such plasmid-borne genetic modules were also known as "addiction modules" because they cause the bacterial host to be "addicted" to the continued presence of the genetic element. Homologs of these extrachromosomal addiction modules were recently discovered on the chromosome of Escherichia coli and other bacteria through the analysis of completed genome sequences.
We have identified a putative PCD module encoded on the endogenous pRA2 plasmid of Pseudomonas alcaligenes NCIB 9867 that shared structural homology with the ζ toxin of the Streptococcus pyogenes plasmid pSM19035 εζ addiction module. Structural homologs of εζ have also been identified on the chromosomes of microbial pathogens such as Streptococcus pneumoniae and Enterococcus faecalis. We have studied in depth the molecular biology of the pRA2 plasmid in Pseudomonas alcaligenes NCIB 9867 especially its replication, transfer and plasmid partitioning. This project intends to further characterize, at the molecular level, the homolog on pRA2, and use it as a model to investigate similar homologs in the genome of Streptococcus pneumoniae.
Principal Investigators at MUST
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