A new study describes new insights into Legionella pneumophila, the bacteria responsible for most cases of Legionnaires' disease. This report investigates the genetic background of L. pneumophila, provides clues to the evolution and emergence of this pathogen, and describes the identification of a worldwide-distributed epidemic clone.
Legionnaire's disease is characterized by severe pneumonia, afflicting the elderly and individuals with weakened immune responses in particular. While L. pneumophila, a genetically diverse species and one of many Legionella species, is common in natural and drinking water supplies, the majority of Legionnaire's disease cases worldwide (approximately 84%) are caused by a single serogroup, L. pneumophila Sg1. Recent work has suggested that even though Sg1 is responsible for most clinical cases, this serogroup accounts for only about 30% of environmental Legionella.
As the prevalence of Sg1 in Legionnaire's disease cases does not appear to be a result of environmental predominance, the frequent occurrence of Sg1 in disease is likely due to higher virulence. In this study, researchers led by Dr. Carmen Buchrieser of the Institut Pasteur conducted a comparative genomics analysis to gain insight into the basis for the higher virulence of Sg1.
To compare Sg1 and other Legionella isolates, the researchers constructed DNA-arrays containing genes known to be variable in L. pneumophila strains, including a set of known and potential virulence genes. "We screened the gene content of 217 L. pneumophila strains and 32 other Legionella (non-pneumophila) strains that were isolated from humans and the environment," describes Buchrieser. "We discovered core virulence- and eukaryotic-like genes are highly conserved, indicating strong selection pressures for their preservation."
Importantly, a cluster of lipopolysaccharide (LPS) biosynthesis genes was found to be common in Sg1, even in different genetic backgrounds. This suggests that the gene cluster could be transferred horizontally between strains. "The LPS of Sg1 itself may confer to Sg1 strains the high prevalence in human disease," explains Buchrieser. Variation in LPS, a component of the cell wall normally recognized by the innate immune system, could allow the bacteria to evade host immune responses.
Most significantly, this study identified a specific clone of Sg1 that is present in both sporadic cases and outbreaks worldwide. "The identification of this clone opens exciting possibilities of research to find out which genes contribute to improved interaction with the host, or to improved fitness in the environment, or to both," describes Buchrieser.
Buchrieser cautions that there may be other genetic factors involved in the emergence of an epidemic strain. "Although the strains carrying this LPS cluster seem to be particularly adapted for causing human disease, additional genetic factors present in the genome may have allowed a particular clone of Sg1 to evolve within this highly diverse species."
In addition to gaining insight into the genetic basis for L. pneumophila Sg1 virulence, Buchrieser suggests this work may lead to new methods of detection. "The findings of this comparative genomics approach will be invaluable for the development of novel tools to rapidly detect Legionella-associated risk factors in water distribution systems of hospitals and other potential sites for Legionella infection."
Scientists from the Institut Pasteur/Centre National de la Recherche Scientifique (CNRS) (Paris, France) and the Centre National de Référence des Legionella/Institut National de la Santé et de la Recherche Médicale (INSERM) (Lyon, France) contributed to this study.
This work was supported by grants from the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS), the Agence française de sécurité sanitaire de l'environnement et du travail (Afsset), and the Israeli-French Research Networks Program in Bioinformatics.
The manuscript will be published online ahead of print on Wednesday, February 6, 2008. Its full citation is as follows: Cazalet, C., Jarraud, S., Ghavi-Helm, Y., Kunst, F., Glaser, P., Etienne, J., and Buchrieser. C. Multi-genome analysis identifies a worldwide distributed epidemic Legionella pneumophila clone that emerged within a highly diverse species. Genome Res. doi:10.1101/gr.7229808.
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