Unravelling bacterial pathogenesis
Streptococcus pneumoniae is a major human pathogen that can be present in nearly 60% of the population with no apparent symptoms. The bacterium can switch to a pathogenic state, gain access to the blood and cause meningitis and pneumonia. To achieve this, S. pneumoniae turns on the expression of certain virulence factors such as pneumolysin, a well-characterised toxin. The ply gene encodes pneumolysin and it has a well-conserved sequence among different clinical isolates. At high concentrations, pneumolysin makes holes in the cell membrane and ruptures infected cells while at low concentrations it triggers inflammation. Paradoxically, pneumolysin is produced within the bacterium and can only reach the host cell after lysis. This means that if all bacteria lyse, then the population would fail to propagate suggesting the existence of mechanisms for the controlled release of pneumolysin. Recent evidence suggests that only part of a bacterial population undergoes lysis as a form of self-destructive cooperation. The EU-funded 'Regulation of pneumolysin in the human pathogen Streptococcus pneumoniae: A single cell approach' (PNEUMO-CELL) project worked on devising analytical tools for studying the mechanism of self-destructive cooperation in S. pneumoniae. In this context, researchers developed fluorescent proteins, flow cytometry assays and time-lapse microscopy protocols for visualising S. pneumoniae at the single cell level. They discovered that pneumolysin is produced by all the cells within a bacterial population. Using time-lapse microscopy, they observed that pneumolysin gets attached to the cell wall and production increases just before lysis. This indicated that the phenomenon of self-destructive cooperation could partly involve transcriptional regulation of the ply gene. Besides locating the promoter of the five-gene operon including the ply gene, scientists also identified five genes with suspected involvement in the transcriptional regulation of ply gene. Taken together, the results of the PNEUMO-CELL project provide important insight into the molecular mechanisms that regulate the production of the toxin, pneumolysin. Understanding the mechanism of microbial pathogenesis will undoubtedly provide solutions for their effective eradication.
Keywords
Streptococcus pneumonia, pneumolysin, ply gene, self-destructive cooperation
