About the
Project
We selected for
sequencing the Legionella pneumophila subsp.
pneumophila (serogroup 1), Philadelphia 1
strain, derived from the original 1976 isolate
(D.W. Fraser et al., J. Med. 297, 1189 (1977)).
The sequence was assembled using a combined
approach. Approximately 8-fold coverage was
obtained from whole-genome shotgun sequences and
5-fold coverage from BAC clone-based shotgun
sequences. A detailed description of the methods
is available at Science
online.
The
complete circular Legionella pneumophila genome
consists of 3,397,754 base pairs (bp).Additional
global details are available by clicking on
current statistics. A 45 kbp
portion of the sequence containing the lvr/lvh
type IV secretion system gene region and
genes potentially involved in recombination,
possesses a higher than average GC content,
implying that it was acquired by lateral
transfer. In addition to its maintenance as
part of the chromosome, this region exists also
an episomal plasmid-like element (pLP45).
We
have predicted approximately 3000 genes,
belonging to 181 pathways as assessed by
PathoLogic (link will be available shortly). Of
the genes with predicted functions, the largest
percentages appear to be involved in metabolic
processes, information transfer or
transport. Nonetheless, there are large
numbers of putative proteins with regulatory,
protective, signal transduction and virulence
functions (a bar graph showing these percentages
is available as Figure S1 at Science
online), which also provides additional
details on the gene complement, along with tables
of previously known and new candidate virulence
factors.
The
genome has a substantial number of expanded gene
families, mainly transporters. A complete
list of gene family expansions is available via
the genome annotation button.
Comparative analysis with completely sequenced
genomes from other g-proteobacteria
and with other intracellular pathogens, suggests
that gene repertoires may be determined as much
by bacterial lifestyle as by evolutionary
relatedness. The most closely related
completely sequenced genome is that of Coxiella
burnetii, a highly infectious pathogen that
causes the disease Q fever and a potential
bioterror agent. Like Legionella, it
is taken up by lung macrophages, but unlike Legionella
which at least temporarily evades lysosomes,
it survives and replicates within this acidic
organelle, perhaps aided by its apparent
possession of a high pI protein complement (R.
Seshadri et al., Proc. Natl. Acad. Sci. U.S.A.
100, 5455 (2003)) . A high percentage of Legionella
genes are found as orthologs in Coxiella,
and a few genes such as EnhA, EnhB,
and the icm/dot complex, seem to be unique
to these two bacteria.
The
presence of a large repertoire, including
expanded families, of genes encoding drug and
heavy metal effluxers, may explain both the
ability of the bacteria to survive within
protozoa that are known to concentrate heavy
metals, and to some extent its ability to survive
in biocide-treated plumbing systems. With
further studies of the genes and proteins of L.
pneumophila and other Legionellae, some may
eventually emerge as targets for drug or vaccine
therapy.
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