A Pathogen’s Biochemical Mesh

An extensive systems biology evaluation of the pathogen Mycoplasma pneumoniae reveals that the bacterium has more sophisticated biochemical circuits than expected of an organism with so few genes. The comprehensive proteomic, transcriptomic, and metabolomic analysis of the pneumonia-causing bacterium sets a new standard for systems biologists seeking to understand the underpinnings of a biological cell. It also provides new information that could help design drugs against the pathogen.

In three back-to-back Science papers (2009, 326, 1235, 1263, and 1268), scientists reveal that M. pneumoniae has “features of transcription controls and protein organization that are much more subtle and intricate than were previously considered possible in bacteria and, in many ways, appear similar to mechanisms in eukaryotes,” Howard Ochman and Rahul Raghavan of the University of Arizona, Tucson, write in an associated commentary.

The bacterium’s sophistication came as a “big surprise,” says Anne-Claude Gavin, a biochemist at the European Molecular Biology Laboratory (EMBL), in Heidelberg, Germany, who led one of the studies, because M. pneumoniae has an especially small genome. With less than 700 genes, its genome is far smaller than that of Escherichia coli, which has about 4,000 genes, typical for most bacteria. The fact that M. pneumoniae achieves such complexity from such a stripped-down genome may make it a new model organism, she adds.

Gavin collaborated with a huge team of researchers, including Luis Serrano at the Catalan Institute for Advanced Research & Study and Peer Bork at EMBL, to obtain a snapshot of protein localization in M. pneumoniae. Using a combination of X-ray crystallography, tomography, and electron diffraction, the team found that proteins such as the ribosome are partitioned away from a rodlike area of the cell essential for infection, even though the bacterium does not possess organelles typically used for segregation. The team also discovered that M. pneumoniae is particularly good at multitasking, possessing many enzymes that can perform a multitude of reactions, leaving “few redundancies” that are often observed in higher organisms, Ochman adds.